Muscarinic cholinergic inhibition of cyclic AMP formation and adrenocorticotropin secretion in mouse pituitary tumor cells.
Cholinergic muscarinic receptors were identified in AtT-20/D16-16 (AtT-20) cell membranes by receptor binding techniques and the effect of carbachol on basal and stimulated cyclic AMP formation and ACTH release was investigated. Carbachol markedly decreased the stimulatory effect of the adenylate cyclase activator, forskolin, on both cyclic AMP formation and ACTH secretion. Carbachol also reduced forskolin-stimulated adenylate cyclase activity. The stimulatory effects of (-) isoproterenol on cyclic nucleotide formation and ACTH secretion were also blocked by carbachol. The inhibitory effects of carbachol on (-) isoproterenol-stimulated cyclic AMP synthesis and ACTH secretion were reversed by the muscarinic antagonist, atropine, and not by the nicotinic antagonist, gallamine. These data suggest that in AtT-20 cells, inhibition of ACTH secretion may be regulated by activation of muscarinic receptors coupled negatively to adenylate cyclase.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis*; D007545:Isoproterenol / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*
D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D007545:Isoproterenol