Cgrp calcitonin gene related peptide
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CGRP is a 37 amino acid neuropeptide derived from the calcitonin gene that is widely distributed throughout the body. It was discovered in 1980 when the calcitonin gene was cloned and further research in 1982 revealed CGRP. It exists in two forms, alpha and beta, and binds to a receptor composed of CLR and RAMP1. CGRP is involved in many physiological functions as it is found in the central nervous system, peripheral nervous system, and cardiovascular system. It acts as a vasodilator and plays a role in migraine headaches and nociception.
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5HT widely distributed in:
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As a neurotransmitter in CNS
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In lungs, bone marrow, pineal gland (as a precursor of melatonin)
5- HT is then stored in 5-HT containing cells such as enterochromaffin cells and neurons as co-transmitter together with various peptide hormones such as somatostatin, vasoactive intestinal peptide and substance P
5-HT is stored within storage vesicles, and its uptake at the vesicular membrane by vesicular monoamine transporter (VMAT-2) is inhibited by reserpine.
Degradation occurs through oxidative deamination by MAO, to 5-hydroxyindole acetaldehyde followed by its oxidation to 5-hydroxyindole acetic acid (5-HIAA)
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5-HT Receptors Location: 5-HT, receptors are located mainly in CNS. They function as inhibitory presynaptic receptors (auto receptor) and belong to the family of G-protein coupled receptors linked to adenylate cyclase
5-HT1 : Auto receptors; inhibit serotonergic neural activity in brain.
5-HT1A—present in raphe nuclei and hippocampus; buspirone (antianxiety) may act through these receptors.
5-HT1D/1B—Constricts cranial blood vessels and inhibits release of inflammatory neuropeptides in them; sumatriptan (antimigraine) acts through these receptors.
5-HT2A : Previously D type receptor; most important post junctional receptor mediating direct actions of 5-HT like vascular and visceral smooth muscle contraction, platelet aggregation, neuronal activation in brain; ketanserin blocks these receptors.
5-HT3 : Previously M type receptor; depolarizes neurones by gating cation channels; elicits reflex effects of 5-HT—emesis, gut peristalsis, bradycardia, transient hypotension, apnoea, pain, itch; ondansetron (antiemetic) acts by blocking these receptors.
5-HT4 : Mediate intestinal secretion, augmentation of peristalsis. Renzapride (prokinetic) is a selective 5-HT4 agonist.Central Nervous System : 5-HT is an important neurotransmitter in CNS
5-HT is involved in the regulation of mood, behaviour, sleep, depression, pain perception, sexual activity, thermoregulation
in the hypothalamic control of the release of pituitary hormones.
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This slideshare is about what is autocoid,and differences between harmone and autocoid and had expalined about an example which is an autocoid and also an chemical messenger.and it is also known as happy harmone.
5HT widely distributed in:
GIT enterochromaffin cells (90%)
myenteric plexus where it serves as a prokinetic agent
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platelets where it diffuses inside from plasma by active transport, and is released at the site of damage after platelet aggregation,
In lungs, bone marrow, pineal gland (as a precursor of melatonin)
5- HT is then stored in 5-HT containing cells such as enterochromaffin cells and neurons as co-transmitter together with various peptide hormones such as somatostatin, vasoactive intestinal peptide and substance P
5-HT is stored within storage vesicles, and its uptake at the vesicular membrane by vesicular monoamine transporter (VMAT-2) is inhibited by reserpine.
Degradation occurs through oxidative deamination by MAO, to 5-hydroxyindole acetaldehyde followed by its oxidation to 5-hydroxyindole acetic acid (5-HIAA)
5- HIAA is excreted in urine
Gaddum and Picarelli (1957) classified 5-HT receptors into musculotropic (D type) and neurotropic (M type) on the basis of their blockade by Dibenzyline (phenoxybenzamine) and Morphine.
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5-HT1 : Auto receptors; inhibit serotonergic neural activity in brain.
5-HT1A—present in raphe nuclei and hippocampus; buspirone (antianxiety) may act through these receptors.
5-HT1D/1B—Constricts cranial blood vessels and inhibits release of inflammatory neuropeptides in them; sumatriptan (antimigraine) acts through these receptors.
5-HT2A : Previously D type receptor; most important post junctional receptor mediating direct actions of 5-HT like vascular and visceral smooth muscle contraction, platelet aggregation, neuronal activation in brain; ketanserin blocks these receptors.
5-HT3 : Previously M type receptor; depolarizes neurones by gating cation channels; elicits reflex effects of 5-HT—emesis, gut peristalsis, bradycardia, transient hypotension, apnoea, pain, itch; ondansetron (antiemetic) acts by blocking these receptors.
5-HT4 : Mediate intestinal secretion, augmentation of peristalsis. Renzapride (prokinetic) is a selective 5-HT4 agonist.Central Nervous System : 5-HT is an important neurotransmitter in CNS
5-HT is involved in the regulation of mood, behaviour, sleep, depression, pain perception, sexual activity, thermoregulation
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P Col III B.Ph ANS 2 12-2015
1. The document discusses drugs that act on the autonomic nervous system, including adrenergic and cholinergic drugs.
2. It describes the divisions of the autonomic nervous system as the sympathetic and parasympathetic nervous systems. The main neurotransmitters are acetylcholine and adrenaline.
3. Adrenergic drugs like adrenaline can act on alpha and beta adrenergic receptors. Alpha receptors are divided into alpha1 and alpha2 subclasses. Beta receptors are divided into beta1, beta2, and beta3 subclasses. Activation of these receptors leads to various effects in different tissues.
Second Messenger Systems
The document discusses second messenger systems. It describes how second messengers relay signals from cell surface receptors to target molecules inside the cell. Some key points discussed include:
- Earl Sutherland discovered cyclic AMP (cAMP) as the second messenger for epinephrine and won the Nobel Prize for this work.
- Common second messenger systems include those using cAMP, cGMP, phosphatidylinositol, and tyrosine kinases as secondary messengers.
- G proteins act as transducers between receptors and effectors and are important drug targets.
- cAMP and cGMP have several downstream targets including protein kinases that phosphorylate other proteins and regulate various cellular processes.
G- Protein Coupled Receptors
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.
2. cholinergic drugs 2012
This document discusses cholinergic transmission in the autonomic and somatic nervous systems. It notes that acetylcholine is the main neurotransmitter and describes the cholinergic fibers involved in the peripheral and central nervous systems. These include preganglionic autonomic fibers, somatic motor fibers to skeletal muscles, and some postganglionic fibers. The document also summarizes the synthesis, storage, release, and termination of acetylcholine, as well as the two main types of cholinergic receptors: muscarinic and nicotinic receptors.
Marie-Laure Rives Allostery Functional Selectivity KOR Columbia University
The document discusses G protein-coupled receptors (GPCRs) and their modulation by signaling molecules and allosteric modulators. It focuses on the dopamine D2 and adenosine A2A receptors, describing how their heterodimerization was detected ex vivo in the striatum using proximity ligation assays. The document also discusses the therapeutic potential of kappa opioid receptor ligands and developing functionally selective ligands that activate signaling pathways for therapeutic effects but not adverse effects. Specifically, it describes developing G protein-biased kappa agonists like 6'GNTI that do not recruit arrestin in order to achieve pain relief without dysphoric effects.
Hormones - general features
The document discusses hormones and their mechanisms of action. It describes how hormones can be classified based on their chemical nature, solubility, and location of receptors/type of second messenger used. It distinguishes two main groups of hormones - Group I hormones which are lipophilic and act through intracellular receptors, and Group II hormones which are hydrophilic and act through cell surface receptors and second messengers like cAMP, cGMP, Ca++ or phosphoinositides. Specific examples of hormones that fall under each group are provided, along with details of their mechanisms of action and downstream effects.
Insect Neurotransmitters and Receptors by B. Adhikari
Its a brief ppt describing about the type of neurotansmitters in insect synapse and their respective receptors. It also sketches about the synaptic transmission in insect nervous system
Receptors
This document discusses different types of receptors. It describes G-protein coupled receptors (GPCRs) in detail, including that they are the largest group of receptors, mediate many physiological processes, and are targets for around 45% of drugs. It provides examples of specific GPCRs like muscarinic, adrenergic, histamine, dopamine, opioid, and serotonin receptors and discusses their functions. The document also briefly summarizes ligand-gated ion channels, enzymatic receptors, and nuclear receptors. In summary, it provides an overview of the main receptor types, with a focus on GPCRs, their examples, signaling pathways, and physiological roles.
Cell signaling3
The document summarizes G protein-coupled receptor (GPCR) signaling. It discusses how different GPCRs are coupled to different G proteins that activate various downstream effectors like adenylyl cyclase, phospholipase C or ion channels. It provides examples of specific GPCRs like beta-adrenergic receptors and muscarinic acetylcholine receptor and their signaling mechanisms. It also describes the role of second messengers like cAMP, IP3 and DAG in GPCR signaling.
Cellular Neuroscience Products
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G protein coupled receptors
G protein coupled receptors in which you will learn about basic structure and mechanism of GPCR family and their pathway
Third messanger
1. Cellular signal transduction involves signaling molecules, receptors, and intracellular signal transduction pathways that allow cells to respond to changes in their external environment.
2. Signaling molecules like hormones, neurotransmitters, cytokines, and gas molecules bind to membrane or intracellular receptors to activate downstream signaling pathways.
3. The main intracellular signaling pathways include the cAMP/PKA pathway, Ca2+/PKC pathway, cGMP/PKG pathway, and tyrosine kinase pathways which result in phosphorylation of target proteins and regulation of gene expression.
Signal transduction
Cellular signal transduction involves signaling molecules activating receptors on target cells to initiate intracellular responses. There are various types of signaling molecules including proteins/peptides, amino acid/fatty acid derivatives, and steroids. These molecules bind to membrane receptors and induce intracellular second messengers like cAMP, IP3, Ca2+ that activate pathways culminating in altered gene expression, metabolism, or other biological effects. The document provides details on different receptor types, intracellular signaling pathways, and examples of signaling molecules that activate them.
UPDATES OF RENIN ANGIOTENSIN SYTEM INTERVENTION
The Renin-Angiotensin Aldosterone System (RAAS) is the most potent vasoconstrictor system in the body. It was first discovered in the 1930s through experiments clamping renal arteries, and its key components - renin, angiotensinogen, angiotensin I, angiotensin converting enzyme (ACE), angiotensin II, and aldosterone - were delineated over the following decades. Angiotensin II acts through AT1 and AT2 receptors to regulate blood pressure, sodium balance, and other functions. Local tissue RAS systems also exist and are important therapeutic targets.
G protein coupled receptor and pharmacotherapeutics
This document provides an overview of G-protein coupled receptors (GPCRs) and their role in cell signaling. It discusses the history and structure of GPCRs, how they interact with G-proteins and secondary messengers like cAMP and IP3 to activate intracellular signaling pathways. These pathways regulate key cellular processes and are targets for drug development to treat diseases. The document also categorizes different classes of GPCRs and summarizes the mechanisms and physiological roles of various secondary messenger systems like cAMP, IP3, and ion channels in signal transduction.
Autonomic nervous system
The nervous system coordinates all body functions and enables adaptation to internal and external changes. It is composed of nerve cells called neurons and supporting cells called neuroglia. The autonomic nervous system regulates involuntary functions like heart rate and respiration. It has three subdivisions: the sympathetic nervous system mobilizes the body during fight or flight, the parasympathetic nervous system enables rest and digestion, and the enteric nervous system controls the gastrointestinal system.
3.17.2010
The document summarizes key aspects of signal transduction pathways involving smooth muscle relaxation. It describes how acetylcholine binds to receptors on endothelial cells, activating a G protein which signals the production of nitric oxide (NO). NO then diffuses into the smooth muscle cell where it binds receptors and activates guanylate cyclase, increasing cGMP levels. cGMP activates protein kinase G, which phosphorylates calcium channels and causes them to close. With reduced calcium levels, the smooth muscle relaxes. The document also provides an overview of different receptor types, molecular switches in pathways, and differences between heterotrimeric and small G proteins.
Cardiac Biochemistry.pptx
Cardiac enzymes and biomarkers can help diagnose a myocardial infarction. Creatine kinase peaks within 24-30 hours and returns to normal in 2-4 days. The CK-MB isoenzyme is specific to cardiac muscle. Aspartate transaminase and lactate dehydrogenase peak at 24 hours and 48 hours, respectively, and return to normal within a week. Troponins remain elevated for 1-14 days, making them useful biomarkers for detecting heart muscle damage. Measuring multiple enzymes over time provides physicians with a window into when cardiac injury occurred.
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2 GPCR overview.pdfunderstanding of the the role of G coupled receptors
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Marie-Laure Rives Allostery Functional Selectivity KOR Columbia University
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Cgrp calcitonin gene related peptide
- 1. CGRP-Calcitonin Gene Related Peptide Presented by Vijay Anand M. Pharmacy (2nd sem)
- 2. Introduction o 37 amino acid vasoactive neuropeptide o Derived from CT gene localized in chromosome 11 o Widely distributed in CNS, PNS, CVS o 2 forms- α and β CGRP o α- CGRP found in neuronal tissues and a potent vasodilator
- 4. Discovery o Canadian scientist Copp postulated the existence of calcium lowering peptide-CT o 1961- regulation of parathyroid hormone o Found 2nd calcium regulating hormone- CT o 1980- CT gene was cloned o 1982- CGRP was discovered by molecular cloning of CT gene
- 7. Distribution o CNS - nervous system and discrete brain areas - co-exists with acetylcholine - most neurons, both CGRP co-exist but β- CGRP is predominant in enteric nervous system and pituitary gland o PNS - present in sensory ganglia often stored with substance P
- 9. Receptors o Heteromeric receptor composed of a G protein- coupled receptor called calcitonin receptor-like receptor (CALCRL) and a receptor activity-modifying protein (RAMP1). o CGRP receptors are found throughout the body o may modulate a variety of physiological functions in all major systems -respiratory, -endocrine, -gastrointestinal, -immune, and -cardiovascular.
- 10. Functions o Role in CNS - modulate acetylcholine receptor function o Role in PNS - modulate antigen presentation in Langerhans cells - block tolerance to morphine - potent inhibitor of gastric acid secretion o Role in CVS - potent vasodilator, positive ionotropic and chronotropic effect o Headache and nociception o CGRP is known to be closely involved in the cascade of events that lead to a migraine attack.
- 11. Thank you