The FASEB Journal, Vol 1, 119-124, Copyright © 1987 by The Federation of American Societies for Experimental Biology

RESEARCH COMMUNICATIONS

Enhanced cAMP accumulation after termination of cholinergic action in the heart

J Linden

Cholinergic agents decrease myocardial contractility in part by inhibiting adenylate cyclase (EC 4.6.1.1) activity. We have found that after a prolonged preincubation period (greater than 6 h), washout of cholinergic agents from embryonic chick hearts or cultured heart cells results in a persistent increase in their basal and catecholamine- stimulated cAMP content. Membranes prepared from pretreated cells have elevated basal, forskolin-, and catecholamine-stimulated adenylate cyclase activities. This myocardial adaptation to cholinergic agents is analogous to changes in nerve cells and other cell types after prolonged exposures to narcotics or other inhibitors of adenylate cyclase, respectively. A rapid (less than 5 min) adaptation response to cholinergic agents can also be demonstrated in heart cells by quickly blocking agonist action with atropine. Atropine alone has no effect, but after a brief preincubation period with agonists (methacholine or oxotremorine), the addition of atropine transiently enhances catecholamine-stimulated cAMP accumulation by 2.5-fold. These responses are absent in heart cells pretreated with pertussis toxin. The data indicate that the response is not mediated by the phosphoinositide pathway, which has been demonstrated to be insensitive to pertussis toxin in chick heart. Enhanced cAMP accumulation after termination of muscarinic agonist action may provide an explanation for the observation that acetylcholine sometimes produces biphasic contractile responses.

This article has been cited by other articles:

				E. N. Dedkova, X. Ji, Y. G. Wang, L. A. Blatter, and S. L. Lipsius Signaling Mechanisms That Mediate Nitric Oxide Production Induced by Acetylcholine Exposure and Withdrawal in Cat Atrial Myocytes Circ. Res., December 12, 2003; 93(12): 1233 - 1240. [Abstract] [Full Text] [PDF]

				S. L. Thomas, R. S. Chmelar, C. Lu, S. W. Halvorsen, and N. M. Nathanson Tissue-specific Regulation of G-protein-coupled Inwardly Rectifying K+ Channel Expression by Muscarinic Receptor Activation in Ovo J. Biol. Chem., November 21, 1997; 272(47): 29958 - 29962. [Abstract] [Full Text] [PDF]

				Y.G. Wang, J. Huser, L.A. Blatter, and S.L. Lipsius Withdrawal of Acetylcholine Elicits Ca2+-Induced Delayed Afterdepolarizations in Cat Atrial Myocytes Circulation, August 19, 1997; 96(4): 1275 - 1281. [Abstract] [Full Text]

				Y. G. Wang and S. L. Lipsius A Cellular Mechanism Contributing to Postvagal Tachycardia Studied in Isolated Pacemaker Cells From Cat Right Atrium Circ. Res., July 1, 1996; 79(1): 109 - 114. [Abstract] [Full Text]

				Y. G. Wang and S. L. Lipsius Acetylcholine Elicits a Rebound Stimulation of Ca2+ Current Mediated by Pertussis Toxin–Sensitive G Protein and cAMP-Dependent Protein Kinase A in Atrial Myocytes Circ. Res., April 1, 1995; 76(4): 634 - 644. [Abstract] [Full Text]