Cholinergic inhibition of catecholamine-stimulable cyclic AMP accumulation in murine atria.
Carbachol antagonizes isoproterenol-stimulable cyclic AMP accumulation in mouse atria by direct activation of cardiac muscarinic receptors. Inhibition by carbachol occurs rapidly and is completely reversed when the drug is removed. Neither nitroprusside nor 8-bromo-cyclic GMP mimics the actions of carbachol and low concentrations of carbachol block cyclic AMP accumulation without increasing the intracellular cyclic GMP content. Carbachol does not block cyclic AMP accumulation by activating phosphodiesterase since it is fully effective in the face of marked phosphodiesterase inhibition, nor does it appear to inhibit the catalytic activity of adenylate cyclase since it does not decrease either basal or cholera toxin-stimulated cyclic AMP accumulation. The interaction between carbachol and isoproterenol is not competitive, since cholinergic inhibition cannot be surmounted by increasing concentrations of isoproterenol. The site of muscarinic action therefore appears to involve the mechanisms coupling the hormone-receptor complex to adenylate cyclase. This site is distinct from that of cholera toxin action since there is no antagonism between the effects of cholera toxin and carbachol on cyclic AMP metabolism in the atrium.
D015124:8-Bromo Cyclic Adenosine Monophosphate; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000378:metabolism
D010726:Phosphodiesterase Inhibitors; D011976:Receptors, Muscarinic; D009599:Nitroprusside; D015124:8-Bromo Cyclic Adenosine Monophosphate; D002217:Carbachol; D002772:Cholera Toxin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D006152:Cyclic GMP; D007545:Isoproterenol