Constitutive inhibitory action of muscarinic receptors on adenylyl cyclase in cardiac membranes and its stereospecific suppression by hyoscyamine

0142311 - FGU-C 20020033 RIV CZ eng J - Journal Article
Říčný, Jan - Gualtieri, F. - Tuček, Stanislav
Constitutive inhibitory action of muscarinic receptors on adenylyl cyclase in cardiac membranes and its stereospecific suppression by hyoscyamine.
Physiological Research. Roč. 51, č. 2 (2002), s. 131-137. ISSN 0862-8408. E-ISSN 1802-9973
R&D Projects: GA AV ČR IAA7011910; GA ČR GA309/99/0214
Institutional research plan: CEZ:AV0Z5011922
Keywords : muscarinic receptors * adenylyl cyclase * constitutive activity of receptors
Subject RIV: FR - Pharmacology ; Medidal Chemistry
Impact factor: 0.984, year: 2002

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 ofthe 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.
Permanent Link: http://hdl.handle.net/11104/0040017