<prompt> Histamine acts on-G protein coupled receptorsLigand gated ion channelsEnzyme linked receptorsIntracellular recepters  <response>: 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 ACo 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, DopamineD1, 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 Ca2 from intracellular organelles - increased cytosolic Ca2. DAG enhances Protein Kinase C activation by Ca2. Ca2 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, ADHVasopressin 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 Nao Examples - 1 Ca2-b1-adrenergic, 2 Ca2-DopamineD2, GABAB, 3 K -Adrenergic -a2, muscarinic M2, DopamineD2, GABAB. 