G protein-coupled receptors (GPCRs) are a large family of receptors that span cell membranes and activate intracellular signaling pathways in response to extracellular stimuli. They are activated by a wide range of ligands including light, hormones, and neurotransmitters. Upon ligand binding, GPCRs activate heterotrimeric G proteins, which then initiate intracellular signaling cascades. The three main G protein families - Gs, Gi, and Gq - activate or inhibit different downstream effector enzymes to elicit a cellular response. Dysregulation of GPCRs and their associated signaling pathways can lead to various diseases.
MAPK Signaling pathway (Mitogen-activated protein kinase), how the pathway helps in regulation of mitosis, It's activation and inactivation inside the cell, roles of MAPK pathway in cancerous cell, different classes of MAP kinase in human
GENERAL IDEA OF SIGNAL TRANSDUCTION
DEFINATION
WHAT DOES THE TERM SIGNAL TRANSDUCTION MEANS
HISTORY
BASIC ELEMENTS IN SIGNAL TRANSDUCTION
TYPES OF SIGNAL TRANSDUCTION
SIGNALLING MOLECULE
RECEPTOR MOLECULE
MODES OF CELL CELL SIGNALING
SECOND MESSENGER
SIGNAL TRANSDUCTION PATHWAY
SOME SIGNALING PATHWAYS
SIGNIFICANCE
CONCLUSION
REFERENCE
GPCRs are the most dynamic and most abundant all the receptors. The G protein-coupled receptor (GPCR) superfamily comprises the largest and most diverse group of proteins in mammals. GPCRs are responsible for every aspect of human biology from vision, taste, sense of smell, sympathetic and parasympathetic nervous functions, metabolism, and immune regulation to reproduction. GPCRs interact with a number of ligands ranging from photons, ions, amino acids, odorants, pheromones, eicosanoids, neurotransmitters, peptides, proteins, and hormones.
Nevertheless, for the majority of GPCRs, the identity of their natural ligands is still unknown, hence remain orphan receptors.
The simple dogma that underpins much of our current understanding of GPCRs, namely,
one GPCR gene− one GPCR protein− one functional GPCR− one G protein −one response
is showing distinct signs of wear.
Introduction
Definition
History
Basic element in signal transduction
Basic Pathway of signal transduction
Types of signal transduction
Second messenger
Pathway of signal transduction
Conclusion
References
MAPK Signaling pathway (Mitogen-activated protein kinase), how the pathway helps in regulation of mitosis, It's activation and inactivation inside the cell, roles of MAPK pathway in cancerous cell, different classes of MAP kinase in human
GENERAL IDEA OF SIGNAL TRANSDUCTION
DEFINATION
WHAT DOES THE TERM SIGNAL TRANSDUCTION MEANS
HISTORY
BASIC ELEMENTS IN SIGNAL TRANSDUCTION
TYPES OF SIGNAL TRANSDUCTION
SIGNALLING MOLECULE
RECEPTOR MOLECULE
MODES OF CELL CELL SIGNALING
SECOND MESSENGER
SIGNAL TRANSDUCTION PATHWAY
SOME SIGNALING PATHWAYS
SIGNIFICANCE
CONCLUSION
REFERENCE
GPCRs are the most dynamic and most abundant all the receptors. The G protein-coupled receptor (GPCR) superfamily comprises the largest and most diverse group of proteins in mammals. GPCRs are responsible for every aspect of human biology from vision, taste, sense of smell, sympathetic and parasympathetic nervous functions, metabolism, and immune regulation to reproduction. GPCRs interact with a number of ligands ranging from photons, ions, amino acids, odorants, pheromones, eicosanoids, neurotransmitters, peptides, proteins, and hormones.
Nevertheless, for the majority of GPCRs, the identity of their natural ligands is still unknown, hence remain orphan receptors.
The simple dogma that underpins much of our current understanding of GPCRs, namely,
one GPCR gene− one GPCR protein− one functional GPCR− one G protein −one response
is showing distinct signs of wear.
Introduction
Definition
History
Basic element in signal transduction
Basic Pathway of signal transduction
Types of signal transduction
Second messenger
Pathway of signal transduction
Conclusion
References
General principles of signal transduction
G Protein-coupled Receptors (GPCRs): Structure and Mechanism.
GPCRs that Regulate Adenylyl Cyclase.
GPCRs that Activate Phospholipase C.
GPCRs that Regulate Ion Channels.
GPCRs that Regulate Gene Transcription.
1.WHAT ARE GPCRs
2. CLASSIFICATION OF GPCRs
3. GPCRs SECOND MESSENGERS
4. GPCRs FAMILIES
5. STRUCTURE IF GPCRs
6. DRUG TARGETS OF GPCRs
7. CONCLUSION
8. REFERENCES
9. THANKS
GPCRs are the largest and most diverse group of integral membrane proteins. These proteins are used by cells to convert extracellular signals into intracellular responses and mediate most of our physiological responses to hormones, neurotransmitters as well as responses to vision, olfaction and taste signal. They mediate most of our and environmental stimulants, and so have a great potential as therapeutic targets for a broad spectrum of diseases. At the most basic level, all GPCRS are characterized by the presence of seven membrane-spanning alpha helical segments separated by alternating intracellular and extracellular loop regions. Coupling with G proteins, they are called seven-transmembrane receptors because they pass through the cell membrane seven times.
CNS Introduction, Neurons, Type of Neurons and functions, Neuroglia and types, Receptors and their types, Synapse, Neurotransmitters and their functions
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
2. G Protein-Coupled Receptors
G protein-coupled receptors (GPCRs), also known
as seven-transmembrane domain receptors, 7TM
receptors, serpentine receptor, and G protein-linked
receptors (GPLR), constitute a large protein family
of receptors that sense molecules outside the cell and
activate inside signal transduction pathways and
ultimately, cellular responses.
They are called seven-transmembrane receptors because
they pass through the cell membrane seven times.
3. The ligands that bind and activate these receptors
include:
Light sensitive compounds
Hormones and
Neurotransmitters
That vary in size from small molecules
to peptides to large proteins.
4. Families of GPCR
3 Families:
A – Rhodopsin family
B - Secretin/Glucagon receptor family
eg. Peptide hormones.
C - Metabotropic Glutamate family
eg. GABAB , Glutamate.
5. Rhodopsin Receptor Family
RLR are a family of proteins comprise of G protein-coupled
receptors and are extremely sensitive to light.
It activates the G protein transducin (Gt) to activate
the visual phototransduction pathway.
Mutation of the rhodopsin gene is a major contributor to
various retinopathies.
6. Remaining receptors are liganded by
known Endogenous compounds.
Examples include receptor (FXR) farnesoid X receptor,
which is activated by bile acid, liver X
receptor (LXR), and peroxisome proliferator-activated
receptor (PPAR).
7. Secretin Receptor Family
The secretin-receptor family of GPCRs
include Vasoactive intestinal peptide receptors and
receptors for secretin, calcitonin and parathyroid
hormone/parathyroid hormone-related peptides.
These receptors activate adenylyl cyclase and
the phosphatidyl-inositol-calcium pathway.
8. Metabotropic Glutamate Family
The metabotropic glutamate receptors (mGluRs) are
family C GPCR that participate in the modulation of
synaptic transmission and neuronal excitability
throughout the central nervous system.
They have been subdivided into three groups, based on
intracellular signalling mechanisms.
Group I mGlu receptors (coupled to PLC and
intracellular calcium signalling).
9. Group II
Group III receptors
are negatively coupled to adenylyl cyclase.
These receptors are generally widely distributed
throughout the mammalian brain with high levels in
the cerebellum and thalamus.
10. Structure of G Protein
G proteins, also known as guanine nucleotide-binding
proteins, involved in transmitting signals and
function as molecular switches.
Their activity is regulated by factors that control their
ability to bind to and hydrolyze guanosine
triphosphate (GTP) to guanosine diphosphate (GDP).
When they bind GTP, they are 'on', and, when they
bind GDP, they are 'off '.
11. G protein complexes are
Made up of alpha (α), beta (β)
and gamma (γ) subunits.
Beta and gamma subunits
can form a stable dimeric
complex referred to as the
beta-gamma complex.
12. G proteins located within the cell are activated
by GPCRs that span the cell membrane. Inside the
cell, on the plasma membrane, G Protein binds GDP
when inactive and GTP when active. When the
GPCRs binds to a signal molecule, the receptor is
activated and changes shape, thereby allowing it to
bind to an inactive G Protein. When this occurs, GTP
displaces GDP which activates the G Protein.
13. The newly activated G Protein then migrates along the
cell membrane until it binds to adenylyl cyclase
which convert ATP to cAMP that leads to the next
step in the pathway and generates a cellular response.
After transduction, G Protein functions as a GTPase
and hydrolyzes the bound GTP which causes a
phosphate group to fall off. This regenerates GDP
and inactivates the G Protein and the cycle repeats.
14.
15. G Protein Mediated Pathways
Secondary messenger Systems Involved In Signal
Transduction:
Adenylate cyclase cAMP mediated pathway
Phospholipase mediated pathway
16. cAMP Mediated Pathway
The cAMP-dependent pathway, also known as
the adenylyl cyclase pathway, is a G protein-coupled
receptor triggered signaling cascade used in cell
communication.
When a GPCR is activated by its extracellular ligand, a
conformational change is induced in the receptor that
is transmitted to an attached
intracellular heterotrimeric G protein complex.
17. Gs cAMP Dependent Pathway
The Gs alpha subunit of the stimulated G protein
complex exchanges GDP for GTP and is released
from the complex.
In a cAMP-dependent pathway, the activated
Gs alpha subunit binds to and activates an enzyme
called adenylyl cyclase, which, in turn, catalyzes the
conversion of ATP into (cAMP).
18. Increases in concentration of the second
messenger cAMP may lead to the activation of an
enzyme called protein kinase A (PKA).
The PKA enzyme is also known as cAMP-dependent
enzyme because it gets activated only if cAMP is
present. Many different cell responses are mediated
by cAMP. These include increase in heart rate,
cortisol secretion, and breakdown of glycogen and
fat.
19. GTP
GDP
GDP
GTP
ATP
cAMP
Cell response
AT
P
Protein
kinase
ADP
Inactive
protein
Active
protein
hormone
Adenylate cyclase
Signaling System
AC
RS
Inhibitor
Ri
20. This pathway can:
Activate enzymes and
Regulate gene expression
If cAMP-dependent pathway is not controlled, it can
ultimately lead to hyper-proliferation, which may
contribute to the development and/or progression
of cancer.
21. Alterations in number, structure or function of receptors
will lead to disorder in cellular signal transduction.
Up-regulation/hypersensitivity
Down-regulation/desensitization
Receptor Gene Mutation
22. Hyperthyroidism
Hyperthyroidism, often called overactive thyroid, is a
condition in which the thyroid gland produces and
secretes excessive amounts of the thyroid hormones
T3 and/or T4. Grave disease is the most common
cause of hyperthyroidism.
23. Mechanism: The thyrotropin receptor (TSH
receptor) responds to thyroid-stimulating hormone
and stimulates the production of thyroxine (T4)
and triiodothyronine (T3). The TSH receptor is a
member of the G protein-coupled receptor and is
coupled to the Gs protein. Mutation in TSHR gene
(chromosome 14q31) lead to the hyperactivation of
cAMP pathway results in hyperactivation of gland
and make progress towards the development of
tumor.
24. Treatment:
Antithyroid Medicine including Propylthiouracil,
Methimazole and Carbimazole.
Radioactive Iodine
25. Cholera Toxin
Cholera is an infection of the small intestine caused by
the bacterium Vibrio cholerae.
Mechanism:
When cholera toxin is released from the bacteria in the
infected intestine, it binds to the intestinal cells
known as enterocytes. Toxin enters, where it activates
the G protein Gs through an ADP-ribosylation
reaction that acts to lock the G protein in its GTP-bound
form, thereby continually stimulating
adenylate cyclase to produce cAMP.
26. Increased Gs activation leads to increased adenylate
cyclase activity, which increases the intracellular
concentration of cAMP to more than 100-fold over
normal and over-activates cytosolic PKA. These
active PKA then phosphorylate the cystic fibrosis
transmembrane conductance regulator (CFTR)
chloride channel proteins, which leads to ATP-mediated
efflux of chloride ions and leads to
secretion of H2O, Na+,K+, and HCO3
- into
the intestinal lumen.
27. In addition, the entry of Na+ and consequently the entry
of water into enterocytes are diminished. The
combined effects result in rapid fluid loss from the
intestine, leading to severe dehydration.
29. Treatment:
Rehydration. The goal is to replace lost fluids and
electrolytes using a simple rehydration solution, oral
rehydration salts (ORS).
Intravenous fluids.
Antibiotics.
Zinc supplements.
30. GicAMP Dependent Pathway
Gi mainly inhibits the cAMP dependent pathway by
inhibiting adenylate cyclase activity, decreasing the
production of cAMP from ATP, which, in turn,
results in decreased activity of cAMP-dependent
protein kinase. Therefore, the ultimate effect of Gi is
the opposite of cAMP-dependent protein kinase.
31. When Gi receptors get activated, they release
activated G-protein βγ- subunits from
inactive heterotrimeric G protein complexes.
Gβγ dimeric protein interacts with GIRK channels to
open them so that they become permeable to
potassium ions, resulting in hyperpolarization of the
cell.
These receptors are primarily found on heart as well as
in brain.
32. Atrial fibrillation (abnormal heart rhythm) is
associated with shorter action potential duration and
believed to be affected by the G protein-gated
K+ channel, IK,Ach.
The IK,AChchannel, when activated by G proteins,
allows the flow of K+ across the plasma membrane
and out of the cell. This current hyperpolarizes the
cell, thus terminating the action potential.
33. In chronic atrial fibrillation there is an increase in this
inwardly rectifying current because of constantly
activated IK,ACh channels. Increase in the current
results in shorter action potential duration
experienced in chronic atrial fibrillation and leads to
the subsequent fibrillating of the cardiac muscle.
Blocking IK,ACh channel activity could be a
therapeutic target in atrial fibrillation and is an area
under study.
34. Opioids are prescribed to treat chronic pain in
different diseases, GIRK channels are activated by
certain GPC opioid receptors, which leads to the
inhibition of nociceptive transmission, thus
functioning in pain relief.
Studies have shown that G proteins directly activate
GIRKs which were found to participate in
propagation of morphine-induced analgesia in
inflamed spines of mice. Research pertaining to
chronic pain management continues to be performed
in this field.
35. GPC Receptors
G Protein Receptors Signaling Pathway
GS
Beta adrenergic
receptors, glucagon,
histamine, serotonin
Increase Adenylyl
cyclase CAMP
Excitatory effects
Gi
Alpha2 adrenergic
receptors, mAchR,
opioid, serotonin
Decrease Adenylyl
cyclase CAMP
Cardiac K+ channel
open- decrease heart
rate
Gq
mAchR, serotonin
5HT1C
PLC- IP3 , DAG
Increase Cytoplasmic Ca
36. Gt
Rhodopsin and colour
opsins in retinal rod
and cone cells
Increase cGMP
phosphodiesterase.
Decrease cGMP
37. Gq Protein Coupled Receptor
Gq protein is a heterotrimeric protein subunit that
activates phospholipase C (PLC). PLC in turn
hydrolyzes Phosphatidylinositol 4,5-bisphosphate
(PIP2) to diacyl glycerol (DAG) and inositol
trisphosphate (IP3) signal transduction pathway. DAG
acts as a second messenger that activates Protein
Kinase C (PKC) and IP3 acts on calcium channels to
release calcium from stores and phosphorylation of
some proteins.
39. Receptors that are Gq protein coupled include:
5-HT2 serotonergic receptors
Alpha-1 adrenergic receptor
Vasopressin type 1 receptors: 1A and 1B
Angiotensin II receptor type 1
Histamine H1 receptor
Metabotropic glutamate receptor, Group I
M1, M3, and M5 muscarinic receptors
40. Clinical Significance
Ligands targeting the mAChR that are currently approved
for clinical use include non-selective antagonists for the
treatment of Parkinson's disease, atropine (to dilate the
pupil), Scopolamine (used to prevent motion sickness),
and ipratropium (used in the treatment of COPD).
41. Pilocarpine can be given in glaucoma because it reduces
intraocular pressure by contraction of the ciliary
muscle, opening the trabecular meshwork and
allowing increased outflow of the aqueous humour
42. Gt Protein Coupled Receptors
Gt protein coupled receptors are found in photoreceptos
(rods and cons) of the eye.
Photoreceptors are light sensitive and responsible for
visual phototransduction process.
These encode a light stimulus as a chemical output.
43. Photoreceptor Cells
Two types of photoreceptors: rods and cones
Rods are very sensitive cells specialized for night
vision.
In bright light conditions the response of the rods is
saturated and cones, faster but less sensitive
photoreceptors, mediate day vision.
44. Phototransduction
Light activates the opsin molecules in the
photoreceptors (rhodopsin). Upon activation becomes
metarhodopsin II.
Metarhodopsin II activates transducin, a Gt protein.
GDP-bound inactive transducin will exchange GDP
for GTP. GTP-bound active transducin will increase
the activity of cGMP phosphodiesterase. The result is
decreased levels of cGMP in the cytoplasm.
45. Decreased levels of cGMP cause the closing of
cGMP-gated ion channels which will lead to
membrane hyperpolarization.
46. Disorders of Phototransduction
Bradyopsia (or ‘slow vision’) is a condition that results
from mutations in genes encoding the transducin-inactivating
protein RGS9 or the RGS9 anchor protein
(R9AP). This protein inactivates transducin during light
termination process.
Patients with bradyopsia have trouble adjusting to
changing light conditions, experiencing a temporary
blindness when first exposed to bright light.
47. Congenital Stationary Night Blindness is an inherited
disorder that affects rod photoreceptors and impairs
vision under low-light conditions.
This disorder may result from missense mutations in
the rhodopsin gene that cause the mutated rhodopsin
protein to constitutively activate transducin.
Persistent activation of the phototransduction cascade
limits the fidelity of the light response by rod
photoreceptors.
48. Retinitis Pigmentosa is an inherited disorder
characterized by degeneration of photoreceptor cells
and accumulation of retinal pigments.
This disorder, which often leads to blindness, can
result from mutations in a variety of genes expressed
in photoreceptors.
49. References
J.M. Baldwin, G.F. Schertler, V.M. Unger, An alpha-carbon
template for the transmembrane helices in the rhodopsin
family of G-protein-coupled receptors, J. Mol. Biol. 272 (1)
(1997) 144–164.
KD Tripati: essentials of medical pharmacology ; 6th edition;
2008.
L.A. Devi, Heterodimerization of G-protein-coupled receptors:
pharmacology,signaling and trafficking, Trends Pharmacol.
Sci. 22 (10) (2001), 532–537.
Wettschureck N, Offermanns S (October 2005). "G proteins
and their cell type specific functions". Physiol. Rev. 85 (4):
1159–204.
50. He C, Yan X, Zhang H, Mirshahi T, Jin T, Huang A,
Logothetis DE (February 2002). "Identification of critical
residues controlling G protein-gated inwardly rectifying K(+)
channel activity through interactions with the beta gamma
subunits of G proteins". J. Biol. Chem. 277 (8): 6088–96.
Xiao X, Wang P, Chou KC (2009). "A cellular automaton
image approach for predicting G-protein-coupled receptor
functional classes". Journal of Computational
Chemistry 30(9): 1414–1423.
Dorsam RT, Gutkind JS. (Feb 2007). "G-protein-coupled
receptors and cancer". Nat Rev Cancer 7 (2): 79–94