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.
Ishikawa
T
T
Department of Pharmacology, University of Tsukuba, Ibaraki-ken, Japan.
Okamura
N
N
Saito
A
A
Goto
K
K
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide; D000242:Cyclic AMP / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology; D009479:Neuropeptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009479:Neuropeptides; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015740:Calcitonin Gene-Related Peptide; D007545:Isoproterenol