Histamine acts on-
Ans. is 'a' i.e., G protein coupled receptors o Histamine acts on G-protein coupled membrane receptors : -i) H1 histaminic receptors - Linked to adenylyl cyclase and act through cAMPii) H2 histaminic receptors - Linked to IP3-DAG system.o Muscarinic receptors (cholinergic receptors) in heart are M2 type. These are responsible for vagus mediated bradycardia.o M2 mediated actions are through cAMP.Mechanism of action of G-protein coupled receptors# This activated G protein effects one of the following effect pathway (activated stimulatory G protein stimulates, or activated inhibitory G protein inhibits) -A) Adenylyl cyclase (AC)o Activation of AC results in increased synthesis and intracellular accumulation of cAMP (by stimulatory G protein). cAMP acts through cAMP dependent Protein Kinase 4 A', which phosphorylate and alters the function of many enzymes, ion channels and structural proteins. Inhibitory G protein inhibits AC and has opposite effects.o Examples - Corticotropin releasing hormone (CRH), FSH, LH, TSH, ACTH (corticotropin), ADH, Vasopressin (V2 receptors), Parathormone, Catecholamines (b2, a2) e.g., adrenaline (most actions), Glucagon, hCG, Calcitonin, Somatostatin, acetylcholine (M2), Dopamine(D1, D2), Angiotensin II (epithelial cells), GABAB, Histamine (H2).B) Phospholipase IP3 - DAG systemo Activation of phospholipase (by stimulatory G protein) hydrolyses the membrane phospholipid phosphatidyl inositol 4, 5 bisphosphate (PIP2) to generate the second messenger inositol 1, 4, 5 - triphosphate (IP3) and diacylglycerol (DAG).o IP mobilizes Ca+2 from intracellular organelles - increased cytosolic Ca+2. DAG enhances Protein Kinase 'C' activation by Ca+2. Ca+2 acts as third messenger in this type of transduction mechanism and mediates the physiological effects of drugs.o Protein kinase-C phosphorvlates various intracellular proteins (threonine, serine or tyrosine residue), causing their activation or inactivation.o Example - Growth hormone releasing hormone (GHRH), Thyrotropin releasing hormone (TRH), GnRh, ADH/Vasopressin (VI receptor, vasopressor action), oxytocin, cholecystokinin, PDGF, Gastrin, Catecholamines (some actions via a1 receptors), A ngiotensin II (vascular smooth muscle), Substance P, Histamine - H1, muscarinic M1, M3C) Channel regulationo Activated G-proteins can open or close ion channels - Ca+ K+ or Na+o Examples - (1) | Ca+2-b1-adrenergic, (2) | Ca+2-DopamineD2, GABAB, (3) | K+ -Adrenergic -a2, muscarinic M2, DopamineD2, GABAB.
G protein coupled receptors
Ligand gated ion channels
Enzyme linked receptors
Intracellular recepters
Chemical Messengers: Receptors