Effects of calcitonin gene-related peptide (CGRP) and isoproterenol on the contractility and adenylate cyclase activity in the rat heart.

The occurrence of calcitonin gene-related peptide (CGRP) has been predicted by the study of the calcitonin gene of rats [1]. Recently CGRP was isolated from porcine spinal cord [3], and thus, CGRP is assumed to be a neuropeptide. It has been shown that CGRP exhibits potent positive chronotropic and inotropic effects on the atrial muscles of rats and guinea-pigs [5, 9, 11] . We have previously demonstrated the presence of nonadrenergic noncholinergic (NANC) nerves in the atria of rats and guinea-pigs [10] and have suggested that CGRP is a neurotransmitter of the NANC nerves in the guinea-pig atria [9, 11]. It is supposed that the positive inotropic response mediated by the beta-adrenoceptor results from a stimulation of the adenylate cyclase (AC) activity and subsequent elevation of cyclic AMP (cAMP) content. In the present study, the effects of calcitonin gene-related peptide (CGRP) and isoproterenol (ISO) on the myocardial contractility and adenylate cyclase (AC) activity were compared in cardiac muscles of the rat. In atrial muscles, CGRP exerted a positive inotropic effect and stimulated the AC activity at the similar dose range. On the contrary, the concentrations of ISO needed to stimulate the AC activity were nearly 10-fold higher than those needed for eliciting positive inotropic responses. In ventricular muscles, CGRP produced neither a positive inotropic responses nor a stimulation of AC activity, while ISO induced both responses. Inasmuch as CGRP-like immunoreactive (CGRP-I) nerves were found to be present in the atria but rarely in the ventricles, CGRP was assumed to be physiologically important in the atria rather than in the ventricles.