Stable cholinergic-muscarinic and alpha-adrenergic inhibition of rat parotid adenylate cyclase.
(-) Isoproterenol-stimulated adenylate cyclase activity of washed at parotid membrane preparations from gland slices previously treated with the alpha-adrenergic agonist, methoxamine, was inhibited approximately 30%. The action of methoxamine required exogenous Ca2+ and was blocked by the alpha-adrenergic blocking agent, phentolamine. Incubation of gland slices with carbamylcholine resulted in a dose-dependent inhibition (50%) of (-) isoproterenol-stimulated adenylate cyclase activity in washed membranes. The action of carbamylcholine was independent of exogenous Ca2+ and was blocked by preincubation with atropine. Cholinergic inhibition of parotid adenylate cyclase was compared to the cholinergic inhibition of adenylate cyclase in dog heart homogenates. While carbamylcholine caused a limited (20-30%) inhibition of basal and (-) isoproterenol-stimulated activities when added to dog heart homogenates, it failed to produce any effect in parotid homogenates prepared in an identical manner. Cholinergic inhibition of parotid adenylate cyclase activity was stable and persisted in washed particulate fractions while the inhibition in dog heart homogenates was reversible by washing. Cholinergic inhibition of adenylate cyclase was markedly dependent on the presence of GTP and was abolished when Mn2+ was subsituted for Mg2+ in both systems. Guanyl-5'-yl imidodiphosphate had little effect on the inhibition in parotid preparations but abolished the inhibition in heart homogenates. It is concluded that, in contrast to the cholinergic action in dog heart homogenates, the exposure of parotid slices to carbamylcholine results in a stable lesion in the adenylate cyclase activity.
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D004285:Dogs; D006160:Guanosine Triphosphate / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000494:pharmacology; D008566:Membranes / Q000201:enzymology; D008729:Methoxamine / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology; D010306:Parotid Gland / Q000201:enzymology*; D051381:Rats
D000067956:Adenylyl Cyclase Inhibitors; D008345:Manganese; D006160:Guanosine Triphosphate; D002217:Carbachol; D008729:Methoxamine; D002118:Calcium