The Role Of G Protein Coupled Receptorss

The Role Of G Protein Coupled Receptorss
On the surfaces of many eukaryotic cells, G protein–coupled receptors (GPCR's) are present. These
receptors are seven trans membrane–spanning, with their N terminal on the exoplasmic face of the
plasma membrane and their C terminal on the cytosolic [1]. GPCR's play a role in intracellular
signalling pathways that result in crucial physiological processes. Cell signalling is an important
process required for cellular activity, coordination and the normal growth and development of cells.
GPCR's transduce extracellular signals allowing them to respond to the extracellular environment
[2]. All GPCR's are coupled to a G protein which is heterotrimeric, meaning it contains three
different G protein subunits: Gα, Gβ and Gγ. When an associated ... Show more content on
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DAG is lipid soluble and so stays in the membrane whereas IP3 is water soluble, so it diffuses
through the cytosol. This signalling pathway therefore splits into two branches with the second
messengers mediating different functions [4]. On one branch is the signalling cascade downstream
of IP3. The IP3 receptors are located on the lumen of the sarcoplasmic reticulum (endoplasmic
reticulum out with smooth muscle cells) and when IP3 is bound they release their intracellular Ca2+
store. This release of intracellular Ca2+ increases the Ca2+ concentration in the cytosol from around
0.1 μM to 1 μM [5]. This changes the physiology of the cell, therefore Ca2+ is said to be a second
messenger itself. The way in which Ca2+ signals is through the binding of proteins. The Ca2+
binding proteins transduce this signal of the cytosolic concentration of Ca2+ and these certain
proteins are called mediator proteins. Such a protein is calmodulin, and is only in its active
conformation when Ca2+ is bound. The increase in intracellular Ca2+ by the binding of IP3 to the
IP3 receptors promotes the binding of Ca2+to calmodulin forming the Ca2+/calmodulin complex.
Proteins that are members of the Ca2+/calmodulin–dependent protein kinase family (CaM kinases)
are activated by Ca2+/calmodulin. It is the formation of this complex that is fundamental for muscle
contraction [4]. Figure 1
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Cell Biochemistry Lab Report
No cell lives in isolation. Cells need to communicate between each other in order for all biological
live on Earth to exist. There are several types of cellular signalling (neural, endocrine, exocrine,
paracrine, autocrine). In most cases signals are released by signalling cells. These signalling
molecules recognise and bind to specific receptors on the target cell. In order for the signal to be
generated in most cases there has to be an environmental change.
Cells detect signals with Cell Receptors on their plasma membrane. The signalling molecule binds
to the Receptor because its shape and chemical complexity. This then activates a chain of reactions
within the cell, leading to a range of different responses. Cells have a mechanism that allows ...
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CXCR4 is widely expressed in T lymphocytes, B lymphocytes, monocytes and macrophages and
others (Sedegh, 2015)). CXCR4 is found mainly in cells if the nerve and immune system where it
interacts with CXCL12. Therefore CXCL12/CXCR4 pathway plays a critical role in antigen
reactions autoimmune response and end–organ inflammation (Sedegh, 2015). CXCR4 is also found
to be highly expressed in several types of cancer like breast, ovarian, prostate and neuroblastoma,
therefore CXCR4/ CXCL12 axis is more and more investigated as important regulator of tumour
progression, angiogenesis, survival and metastasis and represents a crucial target in cancer
treatment. (Sedegh,

Optogenetic Chemogenetics
In the past decade, optogenetic and chemogenetic (Armbruster et al. 2007) approaches have
transformed neuroscience and other disciplines by facilitating the reversible, cell type–specific
control of cellular signaling and electrical activity (Vardy et al. 2015). Chemogenetics and
optogenetics represent 2 emerging approaches to selectively and, unlike traditional gene therapy,
reversibly manipulate cell phenotypes via gene transfer (Jay & Barkin 2014). As complementary
technologies, opto and chemogenetics have demonstrated robust utility for deconstructing the
neuronal codes responsible for both simple and complex behaviors (Deisseroth 2011).
Chemogenetics have dramatically transformed how pharmacologists and systems biologists
deconstruct ... Show more content on Helpwriting.net ...
Adamantidis 2015). It enables tunable manipulation of cell phenotypes using light (Jay & Barkin
2014). The technique employs a set of microbial ion channels and pumps that activate upon
stimulation by particular wavelengths of light. After transgenic expression within neurons, these
type I opsins permit optical modulation of membrane depolarisation or hyperpolarisation with
temporal precision on the order of milliseconds (Snowball & Schorge 2015). The delivery of genes
that encode proteins capable of conveying light sensitivity to neurons has provided a tool that may
overcome some of the limitations of traditional neuromodulation techniques (Henderson et al.
2009). Srivats et al designed a method to optogenetically stimulate and inhibit acute pain in both
normal and pathological states in freely moving nontransgenic mice by intrasciatic nerve injection
of adeno–associated viruses encoding an excitatory opsin enabled light–inducible stimulation of
acute pain, place aversion and optogenetically mediated reductions in withdrawal thresholds to
mechanical and thermal stimuli upon transdermal delievery of optical stimuli. Techniques such as
this, which eliminate the need for surgical implantation of stimulation devices, will obviously have a
tremendous impact on the speed with which optogenetic therapy can

What I Have Learned About Salbutamol
Salbutamol (also known as albuterol in USA) is one of the most famous short–acting β2 agonists. It
has become first line treatment for asthma due to its effectiveness. I met this drug in a dispensing
session in the first term and I think is a good example of what we have learnt so far. In this essay I
will tell you what I know about this drug. Salbutamol is sold in its sulphate form and is marketed as
a racemic product. According pharmaceutical chemistry this means that in it, it has 50% of the R
enantiomer and 50% of the S enantiomer. However, only the R enantiomer is active at the β
receptors. It is thought that the S enantiomer is inactive or causes adverse effects. Because of this,
the pure R enantiomer was marketed – levalbuterol. β receptor agonists are used in the treatment of
asthma and COPD (chronic obstructive pulmonary disease) to relax the muscles in the air passages
in the lungs. Salbutamol is a selective β2 adrenergic agonist, although this selectivity is relative and
dose–dependent. This means that the selectivity is lost at high concentration and thus causing side–
effects. Albuterol has affinity to β 2 receptors and binds to them, causing a relaxation effect. β2
receptors are members of the adrenergic family of receptors and therefore its effects are caused by
an interaction with G proteins. β

Orally Infused Tea
As the cannabis is being orally administered infused in tea, the bioavailability of 4 to 20 per cent. A
previous study has shown that the peak concentration of 20 mg of THC ranges from 4.4 to 11 ng/ml
within 1 to 5 hours, depending on the individual (Huestis, 2009). This amount will provide an
insufficient concentration to raise blood ghrelin levels, therefore, the orally infused tea of 5g
cannabis must be consumed every 30 minutes for x amount of times to increase the blood ghrelin
levels. The 11–hydroxy–THC metabolite will affect the brain at a faster and higher level compared
to its parents compound. This compound elicits the central effects of THC orally and has a half–life
of approximately 12 to 36 hours (Grotenhermen, 2003)
A clinical ... Show more content on Helpwriting.net ...
This results in an increase in appetite and stimulation of catabolic activity, such as glycolysis (Lim
et al., 2013). However, it causes a decline in AMPK activity in the liver and adipose tissue, which
can lead to inhibition of anabolic processes, such as lipogenesis (Kola et al., 2005; Lim et al., 2013).
AMPK also plays a key role in cellular energy homoeostasis in relation to the opposing effects of
leptin and ghrelin in the hypothalamus (Kola et al., 2005). Moreover, the enzyme, AMPK, is
involved in a major pathway associated with the regulation of appetite and metabolism (Kola et al.,

Hippo Pathway Lab Report
Regulation of the Hippo–YAP Pathway by G–Protein–Coupled Receptor Signaling Review Lee
Stunkard Organ size regulation has continued to remain elusive. Recently, the Hippo pathway has
been proposed to be involved in organ size regulation. The Hippo pathway regulates the size of
organs through controlling cell number. A major downstream effector of the Hippo pathway is the
transcription coactivator Yes–associated protein (YAP). YAP is responsible for upregulating genes
that promote cell proliferation and downregulating genes that promote cell apoptosis. Elongated
upregulation of YAP leads to hyperplasia and tumor formation. YAP is inhibited by Lats 1/2 through
phosphorylation of serine 127. When serine 127 becomes phosphorylated YAP binds to ... Show
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Cell growth, migration, proliferation and mRNA levels of YAP regulated genes were tested using
LPA treated cells that had YAP/TAZ knockdown. Cell growth, migration, proliferation and mRNA
levels of YAP regulated genes were all significantly repressed compared to the controls suggesting
that LPA acts through YAP/TAZ. Similar to YAP, TAZ was shown to localize in the nuclear fractions
of cells in immunofluorescence experiments. MST 1/2 and Lats 1/2 levels were tested in response to
LPA treatment. LPA was shown to inhibit Lats 1/2 but not MST 1/2 in immunoblot experiments.
Then to test how LPA and S1P were modulating YAP/TAZ immunoblotting experiments were
utilized. LPA and S1P were found to modulate YAP/TAZ through G–protein–coupled receptor
signaling and Rho GTPases. More specifically, G12/13 receptors appeared to be most involved
while Gq/11 receptors were only slightly involved in dephosphorylating YAP/TAZ. On the other
hand, Gs receptors had the opposite effect, phosphorylating and inhibiting

The Filoviridae Family Corresponds To The Order Of...
The filoviridae family corresponds to the order of Mononegavirales. This growing family of
pathogens are filamentous, enveloped viruses with a genome that is negative–stranded RNA (1
& 2). This family is known to be one of the most pathogenic viruses affecting humans and is mostly
found in bats (their main reservoirs) (3 & 4). It is believed that these viruses are transmitted from
person to person through body fluids or through objects that have been previously contaminated
with body fluids (5). After transmission and incubation period (three to
21 days), the initial symptoms are headache, fever, vomiting and diarrhea. After, the virus may cause
viraemia, coagulopathy, haermoorhagic fever and liver/ multi–organ failure; which in many cases ...
The envelopes of EBOV and MARV are composed of glycoproteins (GP). GP are essential for the
entry of the viruses into the host cell by attaching to its cell surface (10). GP is a homotrimer of GP1
(membrane protein) – GP2 (transmembrane protein) heterodimer linked by disulfide bonds (11 &
12). The mechanism on how GP1 and GP2 drive the introduction of the virus into the host cell is not
well understood yet (7). However, it is known that is characterized by three steps: attachment,
uptake, and membrane fusion (7). GP1 is involved in adhesion of the receptor with the host cell
surface, whereas GP2 is involved in the virus–host cell membrane fusion and entry (13). In most
cases GP1 is believed to bind to different glycosaminoglycans
(GAG) from the host cell i.e. heparin sulfate, to be able to efficiently enter the host cell (2).
GAGs are negative, unbranched polysaccharides found in mostly all cells surfaces but differ in
composition between species (4). It is believed that GAGs are not the only possible way of
attachment for filoviruses to the host surface, meaning that there are other host factors that aid in
viral entry (2). After attachment, virions get into the host cell through micropinocytosis followed by
endosome trafficking which leads to membrane fusion (7). A low pH due to the endosomal events is
what leads to the initiation of membrane fusion (7).
G protein–coupled receptors (GPCR) are the biggest and most diverse family of protein in

Yeast Communication Lab
Purpose In this experiment, we were trying to find out how yeast cells manage to communicate and
thus mate asexually in order to produce offspring. In order for a message to be communicated, a
signal must be sent and then received by another being; this lab will prove how yeast cells go
through this communication process in order to produce a required response for the production of
yeast. Background Information: Both unicellular and multicellular organisms use cell
communication in order to elicit a response which helps an organism coordinate and respond to their
environment. Cellular communication can occur through direct contact, local signaling, or long–
distance signaling. For a response to occur, a message much reach a receptor that ... Show more
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This makes sense, as this is a very secure environment in which yeast can thrive. Although yeast can
reproduce when there is only one reproductive type present, best results are achieved when there is a
mix. It is always better to recombine DNA and increase genetic variability than to have many others
have the same DNA. It leads to a higher survival rate for the species, because one genetic defect
cannot wipe out the entire species. Based on our results we conclude that alpha–type yeast has more
of the mating factor signal released by yeast cells to asexually reproduce because alpha type had a
much higher percentage of budding haploid cells. We also concluded that when alpha and a–type
cultures of yeast are mixed they communicate by both chemical signals and direct contact to
sexually reproduce with each

Opioid Receptors Essay
Opioid receptors can be separated into two different categories: classic and non–classic. Classic
consists of the Mu (), Kappa (), Delta () receptors[15]. While the Non–classic includes only
ORL1[15]. As shown in Figure 9, presynaptic neutrons contain opioid receptors are G–protein
coupled receptors with seven transmembrane helical twist alongside three extracellular and
intracellular loops[15]. Further, G–proteins are typically made of three subunits which include , ,
and . These receptors can be activated by either an endogenous peptide or an exogenous drug that
acts as an agonist[16]. In this case, morphine is an exogenous drug that can mimic the response of
an endogenous peptide such as endorphins[16]. If opioid receptors is inactive, the Ca2+ ion channels
are open which permits the flow of Ca2+ ions into the presynaptic neuron. Simultaneously, the K+
ion channel is closed that prevents any release of K+ ions to the extracellular space. ... Show more
Once an agonist such as morphine attaches itself to the receptor and starts the activation process.
This closes the Ca2+ ion channels and opens the K+ ion channel. The release of K+ ions from the
intracellular space to the extracellular space will yield presynaptic inhibition.[15] The effects of –
opioid receptor activation results in euphoria, sedation, respiratory depression, and pain relief[16].
Once an individual receives extreme amounts on morphine, the body will not be able to manage the
activation or deactivation of the –opioid receptor. This leads to adverse effects on the individual
which includes asphyxia, hallucinations, confusion, delirium, suppressive breathing, and eventually
death[18]. Further, it was determine that the on average the minimum lethal dose for morphine is
200 mg which can lead to life threatening respiratory

Molecular and Cellular Behavior
Signal transduction pathways link signal reception with cellular response
Signal transduction pathways regulate what occurs in, between, and amid individual cells. They are
incredibly crucial because they initiate large responses beginning with a single signal. These
chemical signals are called ligands that enter the cell either through active or passive transport. If the
ligand is small and nonpolar (such as nitric oxide, oxygen gas, and carbon dioxide), then it will
simply diffuse through the cell membrane and will attach to an intracellular receptor. However, if
the ligand does not fit into this category it will attach to a membrane receptor. These ligands are
specific to each receptor. This ensures that no ligand will bind to an incorrect receptor. Once a
receptor is bound, a signal is transduced in a way that the cell can acknowledge it. Signal
transduction pathways will fundamentally affect gene expression, change enzyme or protein activity,
and possibly cell death.
Membrane Receptors
Membrane receptors span the membrane of the cell. Since hydrophilic molecules cannot simply
diffuse through the cells to send a signal to the cell, they must attach to these receptors to be able to
send a signal inside the cell.
Ligand –Gated Ion channel receptor
Specific signal molecules open and close ion channel receptors that permit the passing of ions in and
out of the cell. These ions include Na+, K+, Ca2+, or Cl–, necessary for sending chemical signals.
G–protein–coupled

Type I Taste Biochemistry
Abstract
There are complex molecular mechanisms involved in the sensation of taste, also known as
gustation. They are specific to the five differing taste qualities. Taste transduction involves taste
cells of varying structure and function. These taste cells comprise of type I glial like cells, type II
receptor cells, and type III pre–synaptic cells. Through different mechanisms, the taste receptor cells
detect a respective ligand of sweet, bitter, umami, sour, and salty tastes. It has been suggested that
type I cells are involved in detection and transduction of salt through an ion channel. Type II cells
operate through G–protein coupled receptors that belong to the T1R and T2R families. Neuron
synapses and ion channels aide in the performance of type III cells. Gustatory receptors play an
essential role in the detection and perception of tastes within the oral ... Show more content on
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However, recent evidence suggests an additional ability of detecting salts through ion channels.
Receptor type II cells detect bitter, sweet and umami tastes. They express G protein coupled
receptors (GPCRs) that are associated with gustducin, the G–protein (4). GPCRs are capable of
acting through varying second messenger systems to relay a signal to the interior of the cell. This
signaling produces increased intracellular calcium concentrations. Increases in calcium initiate ATP
release, thus triggering primary gustatory neurons in close proximity to type II cells. Type III taste
cells transduce sour and salty tastes through ion channels (5). Increases in Na+ concentrations for
salt tastes and increases in H+ concentration for sour tastes depolarize taste cells, releasing a
neurotransmitter, for instance serotonin (5). The neurotransmitters released from the cells, such as
ATP or serotonin, activate primary gustatory neurons. Signals are then carried by the axons of
primary gustatory neurons for processing to the gustatory

Evaluation Of Chemokine Receptor Cxcr3 Receptor Gene...
Yahya Bello
To test whether chemokine receptor CXCR3 mediates gene transcription
Introduction
SAA (Serum Amyloid A) function is similar to a C– reactive protein (an annular pentameric protein
that is mostly found in blood plasma and its levels rise in response to inflammation. It considered as
an acute–phase protein of hepatic origin, which increases following interleukin–6 secretion by
macrophages and T cells) but acts as an acute phase protein, which can be used as an indicative,
predictive or as a therapy follow–up marker for many diseases such as Atherosclerosis, Rheumatoid
arthritis, Crohn's disease, and diabetes. As the level of the serum increases, the SAA is triggered by
physical insults to the host which includes infection, trauma, inflammatory reactions, and cancer (R.
Kisilevsky a, 1991). A broad response range is reflected by an SAA gene duplication, which results
into a cluster encoding of several SAA variants and by multiple biological functions of SAA. SAA
prompted chemokines in degrading enzymes through a Toll– like receptors and it functions as an
activator and chemoattractant through a G–protein–coupled receptor. A persistent stimulus in an
infectious or inflammatory area, this will cause the liver to produce more SAA, which will become
an antimicrobial agent by functioning as a direct opsonin of bacteria (Urieli–Shoval, Linke, &
Matzner, 2000). The regulation of innate and adaptive immunity through the helps of SAA benefit
the invention of a better drugs

The Viological Structure Of G-Protein Coupled Receptorss
INTRODUCTION
G–protein coupled receptors (GPCRs) are highly specialised proteins responsible for the
transmission of signals across the cell membrane. They sense signaling molecules such as hormones
and neurotransmitters, and thus play a very important physiological role in the human body
(Venkatakrishnan et al., 2017). GPCRs are also known as metabotropic receptors, which indicates
that they are involved in intracellular signaling.
Scientific Background
The results from numerous research were combined to create a model for the structure of GPCRs
and the heterotrimeric G protein, which aided our understanding of the molecular nature of GPCRs
and its functions. GPCRs are proteins that span the plasma membrane 7 times, hence the name "7 ...
De Lean and Lefkowitz carried out competitive binding experiments to investigate the interaction
between extracellular ligands (both antagonist and agonist), GPCRs and X – a membrane
component.
Method
The antagonist [3H]DHA and the agonist [3H]HBI were incubated with freshly prepared plasma
membranes and appropriate unlabeled ligand for 60 minutes at 25oC. The reaction was stopped by
the addition of ice–cold buffer, and filtered on glass fibre filters. After additional washings with 5ml
of buffer, the concentration of radioactive ligands (antagonists / agonists) trapped on the filters was
measured. Agonist binding is reversible, thus the regular incubation period (60 minutes) was
doubled to ensure that the conditions were compatible with true equilibrium. The binding of
[3H]DHA and [3H]HBI to the frog erythrocyte β–Adrenergic receptor were plotted in saturation and
competition curves.
Results
It had been observed that the binding competition curve for antagonists are steep, and express low
affinity, On the other hand, binding competition curves for agonists are shallow, showing 2 distinct
binding states: high and low affinity state. They discovered that the addition of guanine receptors
could convert the high affinity state to low. This observation was also described in numerous other
GPCRs, such as

Functions Of Immune Defense For The Elimination Of Pathogens
Yahya Bello
Chemokine receptor CXCR3 mediates gene transcription
Introduction
The invasion of microorganisms constantly threatened many organisms and it has evolved systems
of immune defense for the elimination of pathogens in the body (Shizuo Akira1, 2006). Innate and
adaptive immunity are two branches that are comprised in the immune system (Shizuo Akira1,
2006). The innate immune system is the first line of the defense against pathogens and it is mediated
by phagocytes, which includes macrophages and dendritic cells (DC). Adaptive immunity involved
in the elimination of pathogens in the late phase of infection as well as the generation of
immunological memory (Shizuo Akira1, 2006). This type of immunity is characterized by
specificity and develops by clonal selection from a vast range of lymphocytes bearing antigen–
specific receptors that are produced through a mechanism that is generally known as gene
rearrangement. The innate immune response is not entirely specific, but it was rather able to
discriminate between self and a variety of pathogens (Shizuo Akira1, 2006). The innate immune
system identifies microorganisms through a limited number of germline–encoded pattern–
recognition receptors (PRRs). This is large varieties of rearranged receptors utilized by the adaptive
system. PRRs identify microbial components known as pathogen– associated molecular patterns
(PAMPs) and they are important for the survival of the microorganism and are therefore difficult for
the

Allergic Conjunctivitis Research Paper
Allergic conjunctivitis is an inflammatory disease (1) that is initiated by production of pro–
inflammatory mediators including histamine, leukotrienes, and prostaglandins that cause edema and
recruitment of neutrophils, macrophages, and mast cells (2). The infiltrating leukocytes switch from
producing pro–inflammatory mediators to generating the pro–resolution mediators lipoxins,
resolvins, protectins, and maresins (2–5). These compounds actively terminate inflammation by
blocking the effects of the pro–inflammatory mediators on their target tissues including the
conjunctival goblet cells (GC). Annexin A1 is an anti–inflammatory protein originally described as a
mediator of glucocorticoid action (6). This protein binds to the G protein coupled

Homeostasis In The Brain Case Study
The liver is the primary organ for drug metabolism. Any diseases that directly affect on the liver can
alter this process. Some alteration can cause a drug to have more bioavailability, which can cause
toxic effects. Cirrhosis and obstruction jaundice appear to decrease hepatic metabolism and decrease
drug excretion. Another organ function needs to be considered for drug metabolism is thyroid
glands. The activity of metabolizing enzymes in decrease with hypothyroidism and increase with
hyperthyroidism. Impaired liver functions significantly increase the risks if adverse drug effects.
Acute liver impairment interferes with drug metabolism and elimination, while chronic liver
impairment affects all aspects if pharmacokinetic. Consequently, dosage should be reduced for drugs
that are extensively metabolized by the liver. The practitioner needs to assess the degree of hepatic
impairment. Starting therapy with lower doses and monitor liver function ... Show more content on
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Describe the four types of drug receptors and their respective roles in drug action. There are four
types of receptors. The primary function of the receptors is to bind to the ligand. Receptors
recognize specific ligand. Receptors only bind to only one or few ligands and allow them to transmit
a signal into the cell. The common receptors at the cell–surface are Gated Ion Channels,
transmembranous receptors, and G–Protein receptors.
Gated Ion Channels bind a ligand to open or close the channel through the membrane to allow
particular ion to pass through. When the ligand bind to the extracellular at the channel on the cell
surface; the protein structures chance their form and allow ion such as sodium, potassium, calcium
and hydrogen pass through gated ion channels. When the ions pass through the gate, it causes
cellular depolarization. For example, neurons or nerve cells have gate ion channels that are bonded
by neurotransmitter.
G– Protein–Coupled Receptors bind a ligand and activate a protein called

Biochemistry: Transmembrane Receptors
Cells use receptors to recognize a signal, and each signal has a specific receptor ("Cell Signaling").
Receptors bind to signal molecules that act as ligands, molecules that bind to another molecule
which cause the receptor to change shapes ("Cell Signaling"; Urry et al. 109). Receptors are usually
transmembrane proteins located on the plasma membrane which includes enzyme–linked receptors,
ion channel receptors, and G–protein coupled receptors. These receptors use the signals received to
affect the function of the cell without harming the cell. Enzyme–linked proteins are typically
activated by enzymes ("Cell Signaling"). Ion channel receptors open and close, allowing specific
ions to move in and out ("Ion Channel.") An example of an ion channel receptor is a ligand–gated
ion channel which is important for the nervous system. The largest group of transmembrane
receptors are G–protein coupled receptors or GPCRs. GPCRs use a G protein that bind GTP. These
receptors have many functions including embryonic development and helping with taste and smell
(Urry et al. 110). Cells use the receptors on the outside of the cell, but cells also use receptors on the
inside. ... Show more content on Helpwriting.net ...
These receptors are found in the cytoplasm or the nucleus. Before the messenger with the signal can
reach the receptor, it must first be able to pass through the plasma membrane. The signaling
molecules are hydrophobic, which help it pass through the hydrophobic part of the membrane. For
examples, animals have steroid hormones and thyroid hormones that are hydrophobic so the
hormones can go through the plasma membrane. A cell must have the particular receptor in order for
it to be activated. Testosterone can enter cells all over the body, but only the cells with the receptor
will actually use it (Urry et al. 110–111). CLINCHER

Heterotrimeric Meaning Pathway
Describe the signalling pathways downstream of the heterotrimeric G proteins Gs, Gi and Gq.
Heterotrimeric G–proteins are an important group of proteins involved in signal transduction and are
associated with G–protein coupled receptors (GPCR). These proteins bind to guanine nucleotides:
guanosine triphosphate (GTP) and guanosine diphosphate (GDP). Gs, Gi and Gq are the three
different G–protein families that exists.
G–proteins are have three subunits, alpha (), beta () and gamma (), each composed of different
amino acid therefore they are known as heterotrimeric. The G and G are tightly attached to each
other so are known as the beta–gamma complex (G). G subunit has an important feature which is the
binding site for exchange of GTP to GDP.

Types Of Cell Surface Receptors And The Mitogen Activated...
Introduction–
Cell–surface receptors are integral membrane proteins that play a major role in signal transduction,
allowing the function of Neurons, muscles and sensory organs to occur. Their basic function is to
carry out the process of signal transduction by binding to an extracellular signalling molecule. Cell–
surface receptors regulate gene transcription, ion flux in the neurons and growth factors. This
regulation allows the human body to function with little error. They detect the smallest of changes
and respond with a cascade of signalling events appropriately. I am going to describe the four main
types of cell–surface receptors and the Mitogen–activated protein cascade in receptor tyrosine
kinases.
G–Protein Coupled Receptors– ... Show more content on Helpwriting.net ...
GPCRs consist of alpha–helical segments separated by these intracellular and extracellular loops
(Figure 1) Figure 1 Structure of G–protein–coupled receptor, showing alpha–helical proteins
attached to the three subunits of the G–protein.
GPCRs are associated with a G protein, which is heterotrimeric i.e. they consist of three different
subunits: an alpha subunit, a beta subunit, and a gamma subunit (Figure 1). (Scitable by nature) G
proteins are specialized proteins with the ability to catalyse the exchange of guanosine triphosphate
(GTP) and guanosine diphosphate (GDP). (Scitable by nature)
The G–protein receptor is coupled to a trimeric G protein and controls the effector protein. The
receptors activate cytosolic or nuclear transcription via several pathways. They are involved in
signal transduction pathways such as MAP kinase pathway. (Lodish et al.).
When a signalling molecule such as Epinephrine, serotine and adenosine is released and binds to the
extracellular receptor site of the GPCR, the G protein changes conformation and GTP replaces the
GDP on the alpha subunit of the G–protein (Figure 2). This activated alpha subunit then parts from
the beta and gamma subunits. The alpha subunit becomes inactive when the ligand leaves the
receptor site and the receptors own phosphorylase activity removes a phosphate from the GTP
molecule, therefore leaving GDP bound to the alpha–subunit and the reformation of the 3 subunits.
Figure

Second Messenger Research Paper
Second messengers and their actions
Second messengers are intracellular molecules that transmit received signs at receptors on the cell
surface to the target molecules. They also, expand strength of signals.
Second messenger are classified into three major classes:
1) Cyclic nucleotides.
2) Inositol triphosphate IP3 and diacylglycerol DAG.
3) Calcium ions Ca3+.
Common mechanism of second messenger system:
There are several different secondary messenger systems, but they all are quite similar in overall
mechanism, although the substances involved and overall effects can vary.
This conformation change can affect the activity of the receptor and result in the production of
active second messages.
The G–protein is bound to the inner membrane of the ... Show more content on Helpwriting.net ...
Action of cGMP:
It is action is mediated by Protein Kinase G (PKG) , a cGMP–dependent protein kinase, that
phosphorylates target proteins in the cell.
 Inositol trisphosphate (IP3) and diacylglycerol (DAG):
Synthesis of IP3 and DAG:
Peptides and protein hormones like: (vasopressin, thyroid–stimulating hormone (TSH), and
angiotensin) and neurotransmitters like GABA bind to G protein–coupled receptors (GPCRs).
That binding activates the intracellular enzyme phospholipase C (PLC).
The intracellular enzyme phospholipase C (PLC) hydrolyzes phospholipids specifically
phosphatidylinositol–4,5–bisphosphate (PIP2) which is found in the inner layer of the plasma
membrane. this Hydrolysis of PIP2 yields two products:
– Inositol trisphosphate (IP3) .
– diacylglycerol (DAG). 1. Inositol trisphosphate (IP3):
IP3 action:
IP3 is soluble molecule that at first diffuses through the cytosol, then it binds binds to receptors on
the endoplasmic reticulum which as a result cause the release of calcium ions (Ca2+) into the
cytosol.
The final result is elevating in the intracellular calcium which itself triggers the

Mechanism of Melatonin Stimulation of Growth Hormone...
Mechanism of melatonin stimulation of growth hormone release via somatostatin inhibition
Joseph Angelo Israel Peguit
University of the Philippines in the Visayas Cebu College
Natural Sciences and Mathematics Division
Abstract
Secretion of growth hormone is affected by two primary hormones: Growth hormone–releasing
hormone and somatostatin. The former is the primary stimulant to promote growth hormone
secretion while the latter is the primary inhibitor that prevents growth hormone secretion. Many
studies have already shown that melatonin stimulates secretion of growth hormone via somatostatin
inhibition but its mechanisms remain unknown. I hypothesized that melatonin inhibits somatostatin
at transcription level through ... Show more content on Helpwriting.net ...
This means that any regulation of melatonin on other hormones happen mostly in the SCN in the
hypothalamus. The receptors of melatonin belong to the Gi/Go type of the superfamily of G–Protein
Coupled Receptors (GPCR)[8]. The G–proteins are coupled to a number of effector systems
influencing the intracellular signalling. They are designated as Gi/Go type because of their
characteristic being inhibited by the presence of pertussis toxin[8].
Transduction Pathway
The effector systems coupled to the melatonin receptors include the Adenylate cyclase,
phospholipase C, L–type calcium channels, and ATP–sensitive K+ ion channels[8,6,33].
The inhibition of calcium influx via the L–type calcium channels may be mediated by direct
inactivation by the G–protein[6] and/or through induced hyperpolarization by activation of ATP–
sensitive K+ channel[6]. Activation of the G–proteins results to activation of ATP–sensitive K+
channels. The active transport of K+ ion intracellularly results to hyperpolarization of the
membrane. The hyperpolarization inactivates the voltage–sensitive L–type Ca2+ channels which
only opens during membrane depolarization[8,6].
Melatonin receptor activation inhibits activity of Phospholipase C (PLC)[8]. PLC functions to
catalyze hydrolysis of phosphatidyl inositol (4,5) bisphosphate to Inositol triphosphate (IP3) and
Diacyglycerol (DAG). Inositol

What Is The Role Of Mechanisms In The Cells?
In cells, the process of producing and releasing a particular chemical, whether a protein or some
other regulatory molecule, often requires the presence of an external signal. Cells must therefore
have specialized receptors for this signal, or ligand. There are several classes of cell surface
receptors, including receptors with noncatalytic activity, such as G protein–coupled receptors, and
those with catalytic activity such as receptor tyrosine kinases.
The former helps transduce a signal across the plasma membrane through second messenger
systems, including adenylate cyclase. This results in a signaling cascade. First, a signaling molecule
binds to the G protein–coupled receptor, causing the G protein alpha subunit to exchange GDP for ...
Once the necessary transcription factors are activated, the cell initiates transcription of the relevant
gene(s). After transcription and processing in the nucleus, the mature mRNA migrates to the cytosol,
where it is recruited by a ribosome to initiate translation. A series of steps allow the free ribosome to
become associated with the endoplasmic reticulum to allow for the release of the synthesized protein
into the rough endoplasmic reticulum (ER).
First, a signal recognition particle (SRP) binds to the signal peptide as it emerges from the ribosome.
SRP then binds to a receptor on the rough ER surface, which allows the ribosome to bind as well.
Once on the rough ER surface, the ribosome resumes translation and feeds the polypeptide through
the pore and into the rough ER cistern. A signal peptidase, which is associated wit the pore, snips off
the signal peptide. Translation continues, and the growing polypeptide slides into the rough ER
cistern while remaining attached to the ribosome on the surface. The completed polypeptide is then
released into the rough ER cistern, where it floats freely before further processing takes place (Karp
& Patton, 2013).
Processing involves the folding of the protein into its functional three–dimensional conformation.
This folding is aided by molecular chaperones inside the rough ER. Additional modifications may
take place, including attaching short sugar chains to the protein for the formation of glycoproteins
(Karp & Patton,

Behavioral Effects Of Cannabis
Cannabis contains more than 400 different chemicals including phytocannabinoids, terpenoids and
essential oils (ElSohly and Slade, 2005); however, the behavioral effects of cannabis (i.e. euphoria,
relaxation, anxiety, confusion, memory loss, and paranoia) are primarily the result of the
psychoactive ingredient, Δ9–tetrahydrocannabinol (THC) (Adams and Martin, 1996; Wachtel et al.,
2002; Hall and Degenhardt, 2009). The behavioral effects of THC are largely mediated by its action
as a partial agonist at the G protein coupled cannabinoid type 1 (CB1) receptor, which is the most–
abundantly expressed G protein–coupled receptor in the brain. In particular, CB1 receptors have
dense expression in brain regions involved in reward, addiction, and cognitive

G-protein-coupled receptors, also called GPCRs, form the...
G–protein–coupled receptors, also called GPCRs, form the largest receptor family among cell
surface proteins 1. This receptor family is large in size and very diverse, especially in mammalian
genomes 2. In simple terms, GPCRs are used for cellular communication 1. These receptors still
need extensive research since they are such a large, diverse group. More so, continued research can
benefit humans when it comes to pharmaceuticals. GPCRs are key when it comes to cells converting
external signals into the correct intracellular signals 1. There is more than 800 GPCRs within the
human genome. They are responsible for many of our everyday experiences. For example: some our
senses (taste, vision, and smell), "fight–or–flight" responses ... Show more content on
Helpwriting.net ...
Pheromones are molecules released to convey social or sexual cues, done through individuals of the
same species 5. A hormone is a chemical carried via blood to another part of the body (not where it
was synthesized) where it can affect cellular activity 3. With a wide range of ligands that can be
used in the initial step we can see why so many things in our everyday experiences are controlled by
GPCRs. There are hundreds of different GPCRs that control a range of functions within the body.
An example of a GPCR is rhodopsin and protease–activated receptors (PARs). Rhodopsin, a 7
transmembrane (7TM), activates the retinol molecule that is covalently linked in the TM cavity 1.
Rhodopsin does this by changing the configuration to activate the receptor; it changes from cis to
trans 1. PAR is a family of 4 GPCRs that activate important signaling pathways 7. PARs activate
signaling pathways that deal with the following: survival, morphology, release of neurotransmitters,
and activity of ion channels 7. GPCRs are essential in numerous processes through the body (i.e.
immunological function and normal cell growth) 1. Therefore, pharmaceutical drugs are known to
target these G–protein–coupled receptors and this is expected to increase with our knowledge of
GPCRs. Cimetidine is one GPCR drug that blocks the action of Beta–adrenergic receptors (βARs)
and H2 histamine

Relevance Of Study And Scientific Background
Relevance of Study and Scientific Background
G–protein–coupled receptors (GPCRs) are crucial for multiple areas of human physiology including
vision, olfaction, taste, hormone control, and neurotransmitter control (1). As a result of its wide–
spanning functions, it is a popular area of study for therapeutic targets for many diseases (1). GPCRs
are composed of seven –helices that run through the membrane with parts both inside of the cell and
outside of the cell (1).
The widely accepted model for GPCRs work is outlined in Figure 1 of this paper (2) and is essential
for understanding the rest of the paper. An agonist binds to 2AR.Then changes occur to 2AR such
that a Gs heterotrimer complex can bind to the 2AR better. The Gs ... Show more content on
Helpwriting.net ...
T4 lysozymes (T4L) were added to 2AR to stabilize 2AR– Gs. A previous paper referenced by the
Kobilka group (3) used this approach to put T4L between TM 5 and TM 6. In it this Science paper,
they expressed concern about T4L addition modifying WT 2AR. What they found were minimal
differences in the modified 2AR compared to WT (normal antagonist binding and slightly elevated
agonist binding) (3). I would have liked to have seen a similar functional comparison done for the
WT–2AR compared to the T4L modified 2AR for this paper as well for completeness to ensure T4L
addition does not change function. Another problem was the variability in the position of GsAH. A
nanobody (Nb35) was bound to the complex to help reduce this variability. As with T4L addition, I
would have liked to have seen additional data included to show that the Nb35 addition does not
significantly alter the function of the protein complex. While Figure 2c) in the paper shows the
structure of the structure of the 2AR– Gs complex without the aids, I would have liked to have seen
some functional tests performed on the complex, both with the aids for crystallization and without
the aids for crystallization.
A key result of this paper was finding the structure of the active–state of 2AR. To find this, the
agonist–bound receptor of 2AR– Gs was compared to the inactive 2AR. A few differences were
noted. Namely, there is a 14 angstrom movement of TM 6 in the active form compared to

Case Of Failure Of The Data Nodes
case of failure of the data nodes, the name node knows which data node has failed since that
particular data node will not report back in time to the name node. The name node also knows where
the data that is supplied to the data node has gone redundantly to the other data node. Therefore the
job still goes to completion even though a couple of data nodes fail in the big data processing. Since
the Hadoop MapReduce framework is master–slave architecture there is a chance of single point
failure. The single point failure occurs when the name node itself fails. In that case there is also a
presence of secondary name node that place in the event of single point failure.
Figure 1 MapReduce Working
IV. METHODOLOGY/ALGORITHM
.
The action rules discovery is done using the LERS algorithm.
Table 2 – Decision System S Let's apply the LERS algorithm for the decision system S in the table
2. In this example the attributes a, b, c are stable. The attributes e, f, g are flexible and the d is
decision attribute. We will get the action rules when the decision attribute changes from d2 to d1.
Step 1: Extract all rules, which imply  d1 that means we should have d1 on the right hand side of
the rule. This should be done using LERS algorithm.
Step 2: Generate r [d2  d1] r1 = [b1  c1  f2  g1]  d1 r1 [d2  d1] = [b1  c1  (f,  f2) 
(g,  g1)]  (d, d2  d1) b1  c1 – stable f2  g1 – flexible (f,  f2) means change f from
anything to f2
Step 3: Compute set of

Selegiline Research Paper
Selegiline belongs to a class of drugs called phenethylamines. Selegiline is an L–methamphetamine
derivative with a propargyl group attached to the nitrogen atom. This detail is borrowed from
pargyline, an older phenethylamine MAO–B inhibitor.
Selegiline, N–methyl–N–(2–propynyl)–2–methyl–1–phenylethyl–2–amine, is synthesized by the
alkylation of (–)–methamphetamine using propargyl bromide.
2.The muscarinic type being G–protein coupled receptors (GPCRs) that mediate a slow metabolic
response via second messenger cascades, while the nicotinic type are ligand–gated ion channels that
mediate a fast synaptic transmission of the neurotransmitter.
The muscarinic AChRs occur primarily in the CNS, and are part of a large family of G–protein–
coupled receptors ('G proteins'), which use an intracellular secondary messenger system involving
an increase of intracellular calcium to transmit signals inside cells. Binding of acetylcholine to a
muscarinic AChR causes a conformational change in the receptor that is responsible for its
association with and activation of an intracellular G protein, the latter converting GTP to GDP in
order to become activated and dissociate from the receptor. The activated G ... Show more content
on Helpwriting.net ...
The free base form of (S)‑ketamine exhibits dextrorotation and is therefore labelled
(S)‑(+)‑ketamine. However, its hydrochloride salt shows levorotation and is thus labelled
(S)‑(−)‑ketamine hydrochloride. The difference originates from the conformation of the
cyclohexanone ring. In both the free base and the hydrochloride, the cyclohexanone ring adopts a
chair conformation, but the orientation of the substituents varies. In the free base, the o–
chlorophenyl group adopts an equatorial position and the methylamino group adopts an axial
position.[85] In the hydrochloride salt, the positions are reversed, with the o–chlorophenyl group
axial and the methylamino group

Role Of Phosphorylation Of Second Messenger Dependent On...
1. What is the role of the phosphorylation of GPCRs in the process known as "receptor
desensitization?" First describe the process, or what is meant, by the term "receptor desensitization."
What does it mean when we say that the receptor is "uncoupled" versus "down–regulation" of the
receptor? Define and contrast the roles of the "second messenger–dependent" protein kinases versus
the "G protein–coupled receptor" kinases in the process of receptor desensitization. What do the
terms "homologous" versus "heterologous" desensitization refer to? (Ferguson, Pharmacological
Reviews 53:1–24, 2001; Gainetdinov et al., Annual Review of Neuroscience 27:107–144, 2004;
Vasudevan et al., Cell Cycle 10:3684–3691, 2011).
Receptor desensitization: ... Show more content on Helpwriting.net ...
This process called the "uncoupled". "Down regulation" means the receptor mRNA and protein
synthesis decrease and the preexisting receptor degradation. The "uncouple" and "down regulation"
are both involved in the receptor desensitization, but in different steps. These steps are following
described. First, the receptor uncouple from heterotrimeric G proteins; Second, cell surface
receptors internalize into intracellular membranous compartments; Third, receptor mRNA and
protein synthesis decrease result in the down regulation of the total cellular complement of
receptors, as well as both the lysosomal and plasma membrane degradation of pre–existing
receptors. There are two generally kinases which are G protein coupled receptor kinase GRKs and
second messenger–dependent protein kinases(e.g., PKA and PKC). The G protein coupled receptor
kinase only act on the phosphorylate agonist activate receptor. For example, GRK family members
work on activated receptors, and then promote the binding of cytosolic arrestins, which sterically
uncouple the receptor from heterotrimeric G protein. In contrast, second messenger–dependent
proteins kinases act on both phosphorylate agonist–activated GPCRs and other phosphorylates
receptors that have not been exposed to agonist. Thus, agonist–independent phosphorylation can
only happen with the second messenger–dependent protein kinases, but GRKs cannot do it. When
we recognize the

Investigating L2 Learners ' Reanalysis Processes After...
1. Introduction
This proposal aims to investigate L2 learners' reanalysis processes after garden paths (GP). Recent
L1 studies have suggested the lingering first interpretation even after attempts at reanalysis. For
example, when the parser reads the sentence, 'While Anna dressed the baby spit up on the bed', it
often persists in the interpretation 'Anna dressed the baby' despite the globally–correct interpretation
being 'Anna dressed herself' (Christianson et al., 2001). This phenomenon is attributed not to the
incapability of revising the initially assigned interpretation but to the failure in erasing the residual
memory of the interpretation (Slattery et al., 2013). Contrary to L1 reanalysis processes, L2
reanalysis processes remain largely unexplored (e.g. Jacob & Felser, 2016). Thus, this proposal will
address L2 learners' reanalysis processes.
2. Experiment 1 and 2
Experiment 1 and 2 are designed to examine the parser's final interpretation of the object–subject
ambiguity. For this purpose, 48 sentences, exemplified in (1a) and (1b), have been created
(1a). After the mother dressed her son had some lunch at the small table. (GP)
(1b). After the mother dressed, her son had some lunch at the small table. (Non–GP)
The sentence (1a) contains GP and thus requires reanalysis at 'had', whereas (1b) does not due to a
comma placed after 'dressed'. If the parser ends up in the interpretation 'the mother dressed herself'

Dopamine Receptors
INTRODUCTION
In neural signaling, axons transmit trains of action potentials from soma to dendrites, where synaptic
transmission takes place. Until a decade ago it was thought that axonal trunk doesn't play any
important role in neural communication except conducting spikes faithfully. However, it has become
clear that because of the existence of many voltage– and ligand–gated ion channels in the non–
synaptic areas of axons, different neuromodulators, especially monoamines, may have some effects
on the excitability of axonal membrane via activating or deactivating these channels, and therefore,
change the shape or conduction velocity of spikes. Consequently, spikes arriving at the pre–synaptic
terminals may not be exactly the same as those ... Show more content on Helpwriting.net ...
For example, there is an axonal serotonin–sensitive region in the lateral gastric neurons of the crab,
which spikes could be initiated there, propagate to axonal terminals, and change the output of the
neuron. (Meyrand, Weimann, & Marder, 1992) Also, it seems that serotonin via 5–HT1A receptors
could modulate Na+ current, and then inhibit the spike initiation at the axon initial segment. (Cotel,
Exley, Cragg, & Perrier, 2013) In addition, like dopamine, the axonal membrane excitability could
be increased by serotonin in the unmyelinated nerve fibers. (Lang, Moalem–Taylor, Tracey,
Bostock, & Grafe,

Glutamate Receptors
In glutamatergic synapses the neurotransmitter glutamate transmits nerve impulses. Glutamate is the
prevalent excitatory neurotransmitter in the central nervous system (CNS). It can act on two
distinguished receptors: ligand gated ion channels (ionotropic receptors) and G–protein coupled
receptors (metabotropic receptors). In addition, several drugs can interfere with glutamatergic such
as: Riluzole, N–Acetylcysteine (NAC) and Tezampanel.
Synaptic transmission (i.e. the process of information transfer at a synapse) may be accomplished in
two distinguished manners: electrically and chemically. Chemical synapses are the most prevalent
synapses in the human nervous system. Both their synaptic cleft, which is approximately 20–50 nm
wide, and the ... Show more content on Helpwriting.net ...
Nonetheless, all these subtypes express a common basic structure, i.e. the presence of four
hydrophobic regions (TM I, TM II, TM III and TM IV), an extracellular N–terminus and an
intracellular C–terminus (Bristol.ac.uk, 2015). NMDA receptors are formed by two distinctive
subunit families: GluN1 and GluN2. GluN1 is a fundamental component of all NMDA receptors and
it binds to one of the four GluN2 subunits (GluN2A–D). This means that NMDA receptors located
in different parts of the brain may have different pharmacological and biological properties and may
as well act differently. Furthermore, in order for the NMDA receptor to fully work it requires
glycine (co–agonist in this case) to bind to the GluN1 subunit and glutamate to bind to the GluN2
subunit. On the other hand, AMPA receptors are formed by subunits of GluA1–4 while kainate
receptors are formed by GluK1–3 and GluK4,5 subunits and are essential for synaptic plasticity (i.e.
changing the strength of synapses, which might be linked to memory and learning). Furthermore,
AMPA receptors and kainate receptors mediate fast excitatory transmission while NMDA, which
usually coexist with AMPA receptors, mediate a slower excitatory transmission (Bristol.ac.uk,

Hypertension : Hypertension And Essential Hypertension Essay
Hypertension is widely considered to be one of the most important risk factors of cardiovascular
diseases (angina, arrhythmia, etc.). It is the second leading disease that causes mortality in the
world. Hypertension is the condition when there is an increase in the force of blood on the walls of
vessels. It can also be defined as an arterial blood pressure that is raised above 140/90 mm Hg
(systolic/ diastolic BP). Hypertension can be classified into Secondary hypertension and Essential
hypertension. When specific cause is evident but heredity, and various physiological parameters
play a role in increasing blood pressure is known as Essential Hypertension. Secondary
Hypertension is one where the cause is known. According to WHO guidelines between 2006 and
2015, deaths due to cardiovascular diseases are expected to increase by 17% while the deaths from
infectious diseases, nutritional deficiencies, maternal and prenatal conditions are projected to
decline by 3%. The main causes of hypertension includes the age ,hereditary, gender, extra weight,
alcohol consumption, stress life, lazy life etc.
Basically, arterial blood pressure (BP) is directly proportional to the product of blood flow (cardiac
output, CO) and the resistance to passage of blood through pre–capillary arterioles (peripheral
vascular resistance, PVR) Hypertension can be caused by either an increase in Cardiac Output (CO)
or by an increase in Peripheral Resistance (PR) BP = CO X PVR
Renin Angiotensin

Comparing The Different Classes Of Glutamate Receptors Essay
Compare and contrast the different classes of glutamate receptors.
Glutamate as a neurotransmitter
In the brain, neurons communicate between each other and with target cells via a great numbers of
chemicals they release, so called neurotransmitters. A signal in the brain is sent from a presynaptic
neuron to a postsynaptic cell through synaptic transmission, allowing the brain to process
information in a rapid way. (Südhof, Starke and Boehm, 2008)
One of the most important transmitters within the vertebrate nervous system for normal brain
function is known to be glutamic acid also known as glutamate. In the mammalian central nervous
system (brain and spinal cord) is acknowledged that almost all excitatory neurons are glutamatergic
and approximately more than 40% of the synapses in the brain release the amino acid glutamate.
(Purves et al., 2001)
The interaction of this major neurotransmitter with different cells in the brain is dependent on
whether the cells express receptors for glutamate on their surfaces, to which they can bind and
activate. (Hu, Ondrejcak and Rowan, 2012)
Glutamate interaction with glutamate receptors plays a role in the efficacy of synaptic plasticity,
which is fundamental for many neurological functions such as memory, learning, behaviour and in
addition during development in the formation of neural connections within the central nervous
system (CNS), thus allowing neurons to communicate with each other (Sundaram, Gowtham and
Nayak, 2012)

Neurological Disorder Essay
WHAT IS EPILEPSY
Neurological disorder
Primarily characterized by repetitive spontaneous seizures
Many different types
Wide range of symptoms that vary from person to person
Characterized by abnormal electrical activity in brain
CAUSES
Caused by abnormal activity in brain cells
Directly influenced by any head injury or family–related condition
Genetic influence: over 500 genes identified which could lead to epilepsy
Head trauma
Tumors
Strokes
Infectious diseases (AIDS, meningitis)
Prenatal Injury
High correlation of epilepsy in older individuals
SIGNAL MECHANISM
Intracellular Ca2+ levels and calcium homeostatic mechanisms stimulate ligand–gated ion channel
receptors
Elevations in Ca2+ levels can cause acquired epilepsy
Glutamate is a ... Show more content on Helpwriting.net ...
rubbing, chewing generalized seizures involve all areas of the brain absence: occur in clusters; blank
staring and subtle movement e.g. blinking tonic: muscles stiffen atonic or "drop: sudden loss of
muscle control clonic: rhythmic jerking of neck, face, arms myoclonic: sudden brief jerking of limbs
tonic–clonic: loss of consciousness, whole body stiffening or jerking
CORRECT MECHANISM glutamate ionotropic receptors: all permeable to Na and K ions alpha–
amino–2,3–dihydro–5–methyl–3–oxo–4–isoxazolepropanoic acid (AMPA kainate N–methyl–D–
aspartate (NMDA) has Ca channel blocked by Mg ions in membrane depolarization, Mg is
displaced and Ca floods cell glutamate metabotropic receptor

Protein Ligand Essay
G Protein Coupled Receptors (GPCR) is one of the largest known class of membrane protein
receptors which constitute more than 1% of the human genome (Xavier et al., 2007). GPCRs are
widely expressed in human body and have an important role in various cell signaling events. Their
functions are diverse in peripheral organs and brain, being such an important receptor in signaling
has made it an attractive target for various disease pathology. Therefore, obtaining ligands of novel
scaffolds by high through put screening on certain receptor families of GPCRs could be a viable
strategy to get a new lead molecule with a better potency and selectivity. GPCRs share a common
structural architecture of seven transmembrane helix with an extracellular ... Show more content on
Helpwriting.net ...
Figure2 illustrates the different pathways by which Gs, Gi, Gq carry out their signaling via
generation of various second messengers. The assays based on the accumulation or formations of the
second messengers or effectors allow the detection and characterization of ligand types such as full
and partial agonist, antagonist, inverse agonist, and allosteric modulators. Figure 2: Signaling
pathway of Gs, Gi, and Gq coupled GPCRs The discovery of physiological functions of 3–
hydroxytyramine (dopamine), a metabolite of the amino acid tyrosine, more than 50 years ago
(Carlsson et al., 1957) resulted in enormous amount of interest and discussion about this
catecholaminergic neurotransmitter. These Dopaminergic neurons are critically involved in
numerous vital central nervous system functions, including voluntary movement, feeding, reward,
sleep, attention, working memory, and learning (Beaulieu et al., 2011). The involvement of
dopamine in various critical functions, its of no surprise that dopaminergic dysfunction is associated
in variety of human disorder particularly CNS related disorders like Schizophrenia, Parkinson's
Disease, Huntington's Disease and Attention Deficit Hyperactivity Disorder (ADHD) etc. Targeting
these receptors using specific agonists and antagonists provides an opportunity to significantly
influence dopaminergic transmission and dopamine–dependent functions by enhancing or blocking
the actions of dopamine.
Figure 3: Dopamine receptor

Pharmacodynamics (Drug Receptors)
Dose of drug administered ABSORPTION DISTRIBUTION Drug in tissues Drug in systemic
circulation Pharmacokinetics Drug metabolized or excreted ELIMINATION Drug at site of action
Pharmacologic effect Pharmacodynamics Toxicity Efficacy PHARMACOLOGY
Pharmacodynamics Actions of drug on the body  Specific to a drug/ class of drugs Interaction with
target sites (receptors/enzymes) Effects at site of action Dose–response relationship Reduction in
symptoms Modification of disease process Unwanted/side effects Drug interactions Inter– and intra–
patient differences Pharmacokinetics Actions of body on the drug  Non–specific, general processes
Absorption from site of administration Distribution to the ... Show more content on Helpwriting.net
...
Effects of ligand produced after a characteristic lag period of 30 mins to several hours  This is the
time required for synthesis of new proteins  Hence gene–active hormones cannot be expected to
alter a pathologic state within minutes 2. Effects of these agents can persist for hours or days after
agonist concentration in the body has been reduced to zero  Main Reason: Relatively slow
turnover of most enzymes & proteins ⇒ They can remain in cells for hours or days after synthesis 
Partially due to high affinity of receptors for hormone ⇒ Slow dissociation of hormone (2) Ligand
– Regulated Transmembrane Enzymes  Receptors are polypeptides Consist of: 1. Extracellular
ligand–binding site 2. Cytoplasmic enzyme/ catalyic domain.   The cytoplasmic enzyme/
catalytic domain may be: › Tyrosine kinase › Serine Kinase › Guanylyl cyclase  Agonist binds to
receptor's extracellular domain  Change in receptor conformation  Two receptor polypeptides
bind together (Inactive monomeric state is converted to an active dimeric state)  Tyrosine residues
in the cytoplasmic domains become phosphorylated  Tyrosine kinase is activated  Binding &
phosphorylation of SH2 domain protein  Activation of various intracellular signalling pathways
 Responses tend to occur over minutes to hours Examples of such receptors › Insulin receptors
› Growth factor receptors  (3) Ligand – gated ion channels

Chlorpromache Research Paper
This week I learnt about chlorpromazine, which is an antipsychotic. It is also used in short–term
management of anxiety, agitation or disturbed behaviour in non–psychotic disorders.
Chlorpromazine is an antagonist of many receptors, which include α1 adrenoceptor, M3 muscarinic
receptor, H1 Histamine receptor, 5HT2 receptor, dopamine D2 receptor and angiotensin II AT1
receptor. This illustrates one of the pharmacology principles, which is selectivity of a drug. A highly
selective drug ('clean drug') binds to only one receptor or molecular target whereas a drug having
low selectivity ('dirty drug') will bind to many targets in the body. Binding upon many receptors can
produce many effects but some effects are not desired. For example, chlorpromazine ... Show more
Morphine mimics endogenous opioids and activates opioid receptors in the central and peripheral
nervous systems. Opioid receptors are G protein coupled receptors which are coupled to Gi protein.
Upon binding of morphine to opioid receptors, it triggers the inhibition of adenylate cyclase enzyme
and ultimately stops the firing of impulses for nociceptive information. After repeated activation of
opioid receptors by morphine, some receptors can be desensitised and binding of morphine to these
receptors can no longer stops the neurotransmission. As a consequence, tolerance to morphine
develops. When a drug is used repeatedly over time, tolerance can develop as the body adapts to the
presence of the drug in the body. Therefore, a higher dose is required to achieve the same desired
effect. For example, for morphine, if tolerance develops, a higher dose is needed in order to attain
the same analgesic effect. Moreover, one of the adverse effects of morphine when it is used for long
term to relieve pain is physical dependence. Dependence develops as a result of tolerance, leading to
a resetting of homeostatic mechanisms that require the continued presence of drug for normal
function. Therefore, if chronic treatment is stopped suddenly or an antagonist is given, withdrawal
symptoms such as nausea, vomiting, diarrhoea, sweating, anxiety can

Nt1320 Unit 4
So, if we take the last input data, from the example above, and split it on "m" then we would have 4
elements: {5 4}{2}{10}{9}{50 41}. If we consider the first to be the point (previous cluster center),
the second to be the weight (number of points assigned), the third element to be the sum of assigned
points per dimension, and the last to be the sum of assigned points per squared dimension, then it is
much easier to create the KMeansInfo variable as shown above. In composite points we do not have
to calculate the pointsTotal and pointSqrTot attributes of KMeansInfo variable, as they are already
given. The r character in key output, as we said before, is a random number that helps us distribute
our data to more reducers. In this case r can take values between 1 and numberOf Reducers/(k). For
example, if our job runs 90 reducers and our k parameter is 3 then each clusters data will be
distributed to a maximum of 30 reducers instead of 1. ... Show more content on Helpwriting.net ...
We also have four formal type parameters that specify the input key, input value, output key, and
output value. The difference here is that we have a restriction: the input key and value parameters
must be the same type of the mapper's output key and value parameter types. Our reducers know not
only the current cluster centers, as the mappers, but also the delta factor that is used in convergence,
since the convergence check is executed in this step. More specifically, as discussed earlier, reducers
take as input key a cluster id and as input valueList the points (in KMeansInfo–type) that share the
same

The Role Of G Protein Coupled Receptorss

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