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European Heart Journal 1991 12(Supplement F):127-131; doi:10.1093/eurheartj/12.suppl_F.127
Copyright © 1991 by the European Society of Cardiology.
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© 1991 The European Society of Cardiology

Beta-adrenoceptor stimulation-induced increase in cardiac Gi-protein expression and in carbachol sensitivity*

T. Eschenhagen, U. Mende, W. Schmitz, H. Scholz, J. Schultze Am Esch, R. Sempell, A. Warnholtz and J.-M. Wüstel

Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf Martinistr. 52, D-2000 Hamburg 20, Germany

Correspondence: Dr Thomas Eschenhagcn, Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus, Eppendorf, Martinistr. 52, D-2000 Hamburg 20, Germany

Increased plasma concentrations of catecholamines are assumed to be responsible for the decreased sensitivity to catccholamines of the failing heart. We investigated in rat heart the influence of a 4-day infusion of isoprenaline (Iso; 2·4mg.kg–1. d–1), propranolol (Prop; 9·9mg. kg–1.d–1), Iso+Prop or 0·9% NaCl as control (Ctr) on myocardial G1-mRNA and G1-protein levels and on the negative inotropic effect of carbachol in papillary muscles. In Iso-treated rats, hybridization experiments with 32P-cDNAs revealed a 49±18% (n = 7–8) and 27±7% (n = 8) increase in Gt{alpha}.2- and Gt{alpha}.3-mRNA respectively, and pertussis toxin-atalyzed ADP-ribosylotion revealed a 22 ± 7% (n = 8) increase in G1-protein as compared to Ctr. These alterations were accompanied by an increased potency of carbachol (mean EC50: 0·04(µM vs. 0·28 µm) in the presence of Iso in isolated electrically driven (1 Hz) papillary muscles. Prop had no effect on G1-protein expression but antagonized all Iso-induced effects. In conclusion, β-adrenergic stimulation leads to an increased expression of G1 and to an enhanced negative inotropic potency of muscarinic agonists. An enhanced muscarinic receptor coupling via G1 might play a pathophysiological role in heart diseases with increased plasma catecholamine levels.

Key Words: Rat heart • G1-protein expression • β-adrenoceptor • force of contraction

* Dedicated to Professor Dr E. Mutschler on the occasion of his 60th birthday.


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