Adrenoceptor-mediated changes of excitation and contraction in isolated heart muscle preparations.

The inotropic effects of sympathetic stimulation on the heart are mainly ascribed to the activation of beta-adrenoceptors. However, several findings suggest that alpha-adrenoceptors also may help mediate the inotropic response to catecholamines under certain conditions. The onset of the positive inotropic effect mediated by beta-adrenoceptors occurs within seconds and is associated with a faster rate of relaxation. Both beta 1- and beta 2-adrenoceptors are stimulatorily coupled to the enzyme adenylate cyclase, thereby leading to the generation of cyclic AMP. Cyclic AMP increases the slow inward calcium current and enhances the uptake of calcium into the sarcoplasmic reticulum. GTP-binding protein Gs is important for the transmembrane signal transduction. Muscarine and adenosine receptors are inhibitorily coupled to adenylate cyclase, thereby decreasing the inotropic response to catecholamines. Another GTP-binding protein, Gi, is involved in this pathway. The stimulation of the myocardium through the activation of alpha-adrenoceptors seems to differ both qualitatively and quantitatively. Myocardial alpha-adrenoceptors of most species are, if existent, predominantly of the alpha 1-subtype; the functional role of these receptors obviously considerably varies among species.(ABSTRACT TRUNCATED AT 250 WORDS)