Volume 51: 131-137, 2002

Constitutive Inhibitory Action of Muscarinic Receptors on Adenylyl Cyclase in Cardiac Membranes and Its Stereospecific Suppression by Hyoscyamine


Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic and
1Department of Pharmaceutical Sciences, University of Florence, Florence, Italy

Received September 20, 2000
Accepted October 19, 2001

Muscarinic acetylcholine receptors in the heart have been shown to display agonist-independent spontaneous (constitutive) activity which causes changes in the opening of cardiac ion channels and in the activity of G proteins. We investigated whether an inhibition of the constitutive activity of muscarinic receptors induced by the binding of antagonist brings about a change in the synthesis of cyclic AMP in rat cardiac membranes, and whether the action of the antagonist is stereospecific. Atropine and S-(-)-hyoscyamine were indeed found to enhance the forskolin-stimulated synthesis of cyclic AMP in rat cardiac (both atrial and ventricular) membranes by up to 24%. The effect was stereospecific and the potency of R-(+)-hyoscyamine was 30 fold lower than that of the S-(-) enantiomer, confirming that the action of hyoscyamine is receptor-mediated. The effect did not depend on the presence of endogenous acetylcholine in the system used. The results strongly suggest that the adenylyl cyclase in the heart is exposed to continuous mild inhibition by constitutively active muscarinic receptors in the membranes of cardiomyocytes.

Key words
Muscarinic receptors · Adenylyl cyclase · Constitutive activity of receptors · Hyoscyamine · Atropine · Heart · Inverse agonist action

Reprint requests
Dr. Jan Říčný, Institute of Physiology AV ČR, Vídeňská 1083, 14220 Prague, Czech Republic; e-mail

© 2002 by the Institute of Physiology, Czech Academy of Sciences

ISSN 0862 - 8408

Issue 2