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.
This presentation is about the functioning of G-Protein coupled receptors. It also gives necessary information about the G-protein and it functions. It ends by explaining some of the faults associated with GPCR (G-PROTEIN COUPLED RECEPTORS).
RECEPTORS – what are they?
Langley (1878) suggested presence of specific interaction mechanisms/sites after observing SPECIFIC antagonistic interactions between ‘Pilocarpine & Atropine’
RECEPTORS -
Macromolecular PROTEIN/PEPTIDE structures
On the Cell Surface, or Transcellular or Intra-cellular
Have SPECIFIC 3-D structure & Binding properties
Regulate critical Cell Functions – e.g. Enzyme activity Permeability of cell (wall, membrane, etc) Ion Channels activity Carrier functions Template Function, etc.
Monomeric - with separate receptor- & DNA-binding domains
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.
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.
This presentation is about the functioning of G-Protein coupled receptors. It also gives necessary information about the G-protein and it functions. It ends by explaining some of the faults associated with GPCR (G-PROTEIN COUPLED RECEPTORS).
RECEPTORS – what are they?
Langley (1878) suggested presence of specific interaction mechanisms/sites after observing SPECIFIC antagonistic interactions between ‘Pilocarpine & Atropine’
RECEPTORS -
Macromolecular PROTEIN/PEPTIDE structures
On the Cell Surface, or Transcellular or Intra-cellular
Have SPECIFIC 3-D structure & Binding properties
Regulate critical Cell Functions – e.g. Enzyme activity Permeability of cell (wall, membrane, etc) Ion Channels activity Carrier functions Template Function, etc.
Monomeric - with separate receptor- & DNA-binding domains
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.
G-protein (Guanine nucleotide-binding proteins)
Regulatory proteins
Comprise of three subunits (γ), subunits possess GTPase activity.
G proteins belong to the larger group of enzymes called GTPases.
Regaulate guanine nucleotides GDP, GTP.
They bind and hydrolyze guanosine triphosphate (GTP) to guanosine diphosphate (GDP).
They are active 'on' when they are bound to GTP
They are inactive ‘off' when they are bound to GDP
G-Protein Coupled Receptors and Secondary Messenger PathwaysSaikat Polley
GPCR will continue to be highly important in clinical medicine because of their large number, wide expression and role in physiologically important responses. Future discoveries will reveal new GPCR drugs, in part because it is relatively easy to screen for pharmacologic agents that access these receptors and stimulate or block receptor-mediated biochemical or physiological responses.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Factory Supply Best Quality Pmk Oil CAS 28578–16–7 PMK Powder in Stockrebeccabio
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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
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2 Case Reports of Gastric Ultrasound
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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
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.
2. Content
Introduction to receptors
Classification of receptors
Introduction to GPCR faimily
Example of GPCR
Structural feactures of GPCR
Signal transduction pathway
3. Introduction to Receptors
Receptors are the protein structure, which binds drug,
hormone or neurotransmitters to produce biological
action.
LOCATION:- Mostly receptors are present on the cell
membrane and some are present in cytoplasm and
nucleus
LIGAND:- The molecules which binds to receptors called
Ligand. Example Drugs, hormones and neurotransmitters
Latin word Ligare Means “To bind”
4. Introduction to receptors
Type of Ligands
1. Agonist A chemical substances that bind and activate
the receptors to produce a biological action
2. Partial agonist They are agonist that bind and activate
a given receptor but have only partial efficacy at the
receptor relative to full agonist
5. Introduction to receptor
3.Antagonist are the substance that bind and block the
receptor rather than activating it like agonist.
They interfere in natural operation of receptor
(a) Competitive antagonist compete with agonist to bind with
same receptor. They may be reversible or irreversible
(b) Non competitive antagonist They bind to an allosteric site on
the receptor to prevent action of agonist
4 Inverse agonist they binds to same receptor as agonist but
induce a pharmacological action opposite to that of agonist
7. Classification of receptor family
Receptors has been classified into different type
depending on structure and function
1. Present on cell membrane
(a) G protein coupled receptor
(b) Ligand gated ion channel
(c)Receptor tyrosine kinase
2. Present inside cytoplasm
(a)Nuclear receptor
9. G Protein coupled receptor
GPCR is the largest family of cell surface receptor.
About one third of currently available drug acts by binding to
GPCR.
HPCR are responsible for every aspect of human biology from
taste ,vision ,smell,sympathetic and parasympathetic nervous
system ,metabolism and immune system
The name “G-protein coupled receptor” is because these
receptors are coupled with G- protein.
G- protein is Guanine nucleotide (GTP/GDP) binding protein.
12. Structural features of GPCR
All type of GPCR receptors have seven trans – membrane domain ,
connected by three extracellular loops and three Intracellularloops.
So, they are also called 7-Transmembrane helical receptor or
“Surpentine receptors”.
The extracallular region of GPCR posseses N- terminus (NH2) and
binding site.
The intracellularregion of GPCR posseses C- terminus (-CooH) and
interacts G- protein.
Due to binding of G- protein these receptors are called “ G- protein
coupled Receptors.
G- protein are composed of 3 different Subunits ------ α, β and γ
13. Type of G proteins
Since most of the well known function are performed by binding of
Alpha - subunit of G- protein with an effector.
So, on the basis of Alpha – subunit , there are different type of G-
Protein.
G- protein are grouped into 4 faimily
1.Gαi --- Largest & most diverse faimily
i → stand for inhibition of Adenylyl cyclase then increase level of
. cAMP and leads to opening of k+ channels.
2. Gs → Two members in this faimily Gs and G olf
S→ stand for stimulation of Adenylyl cyclase and increase cAMP .
. level and opening of Ca++ channels
Olf – stands for olfactory
3. Gαo→ Inhibition of Ca++ channels.
4. Gαq- phospholipase C activation.
16. Signal transduction process
The different steps involved in signal transduction during activation of G
protein couple receptors include the following—
1. In normal resting state i.e. In the absence of any stimulus/ligand,
guanosine diphosphate (GDP) is bound to the oc-subunit of the G
proteins.
2. Upon activation of receptors by binding of a ligand, there is a
conformational change in Gproteins and GDP dissociates from
oc-β-γ subunit
3. In the meanwhile, GTP associates with the oc-subunit of the G
proteins. In other words ligand binding leads to exchange of
GDP with GTP.
4. The binding of GTP activates the oc-subunit and subsequently,
cx-GTP subunit dissociates from β and γ subunits.
17. Signal transduction process
5. The free oc-GTP subunit binds to the effector/target protein and
modulates its activity depending on the type of G proteins. Gs
stimulates adenylyl cyclase to increase cAMP,opens Ca2+ channels; Gi
inhibits adenylyl cyclase to decrease cAMP, opens K+ channels; Go
inhibits Ca2+ channels; Gq regulates phospholipase-C activity.
6. Due to intrinsic GTPase activity of oc-subunit, GTP is hydrolyzed
to GDP and the resulting oc-GDP complex dissociates from the
effector.
7. The oc-GDP complex reassociates with the β-γ subunit to
complete the cycle. It brings the cell back to normal resting
state.
18. G protein coupled effector system
There are 3 main G protein coupled effector system including adenylate cyclase,
phospholipase C and ion channels
1. Adenylate cyclase: It is a transmembrane enzyme and important effector system. It
has been linked with Gs and Gi protein
Binding of norepenephrine on beta adrenergic receptor in heart
Activation of Gs protein of beta adrenergic receptor
Activation of adenylate cyclase {AC}
Increase cAMP level
Activation of protien kinase A
Opening of ca++ chanells and increase intracellular ca++ level
Increase heart contractility and heart rate
19. G protein coupled effector system
Activation of Gi protein of muscarinic receptor
Inhibition of adenylate cyclase {AC}
decrease cAMP level
Decrease intracellularca++ level
decrease heart contractility and heart rate
21. G protein coupled effector system
2. Phospholipase C It is a membrane linked enzyme
Activation of Gq linked GPCR receptor
Activation of phospholpase C {PLC} enzyme
PLC acts on phospatidyl inositol 4,5 biphosphate [PIP2]
Generation of inositol triphosphate [IP3] and Diacyle glycerol [DAG}
Release of ca++ from endoplasmic reticulam
Physiological action
23. G protein coupled effector system
3. Ion channels
In addition to α subunit, β subunit of G protein ,may also modulate the functioning of
effector.
The most common target for G β-γ subunit is GIRKs {G protien regulated inwardly
rectifying K+ Channel ]
GIRKs cause inward movement of K+ ions
Other targets of G β-γ subunit is Q and N type voltage gated ca++ chanels
