NO EVIDENCE FOR INVOLVEMENT OF DOPAMINERGIC RECEPTORS IN THE POSITIVE INOTROPIC ACTION OF DOPAMINE ON THE ISOLATED RABBIT PAPILLARY MUSCLE

Abstract

Experiments were carried out on the isolated rabbit papillary muscle driven at 0.5 Hz in order to elucidate further the mechanism of the positive inotropic effect evoked by dopamine. The dose-response curve for dopamine was not affected by the antagonists pimozide (10-6 M), yohimbine (10-5 M), pindolol (3 .times. 10-8 M) and phentolamine (10-6 M), when these agents were given separately. Only the simultaneous administration of yohimbine plus pindolol and phentolamine plus pindolol, respectively, shifted the entire curve to the right. This shift was not further influenced by pimozide. Dopamine (10-4 M) increased the cyclic[c]AMP content of the papillary muscle by about 50%; this increase was not affected by pimozide, but was markedly elevated by yohimbine and completely depressed by pindolol. Apparently, dopamine produces its positive inotropic effect through stimulation of myocardial .alpha.- and .beta.-adrenoceptors to about the same degree; stimulation of specific dopaminergic receptors is not involved. The stimulation of .beta.-adrenoceptors was accompanied by an increase of the cAMP level, while that of .alpha.-adrenoceptors was not.