Calcitonin gene-related peptide-induced suppression of atrial natriuretic peptide release through receptors for CGRP1 but not for calcitonin and amylin.

Calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide, is found in the central nervous system as well as in the heart. CGRP shows high sequence homology with amylin, salmon calcitonin, and adrenomedullin. This study aimed to investigate the effect of CGRP on atrial hemodynamics and atrial natriuretic peptide (ANP) release by using isolated perfused beating left atria and to identify its receptor subtypes. Rat alpha-CGRP (0.1, 1, 10, or 100 nM) increased atrial contractility and suppressed the release of ANP in a concentration-dependent manner. However, cys-CGRP (1 microM), a CGRP(2) receptor agonist, slightly decreased ANP release without positive inotropism. Human alpha-CGRP (1 nM) showed an effect on ANP release similar to that of rat alpha-CGRP with potent positive inotropism. However, salmon and rat calcitonin (1 microM) caused a slight decrease or no change in ANP release. Pretreatment with a receptor antagonist for CGRP(1) [rat alpha-CGRP-(8-37)] blocked rat alpha-CGRP-induced suppression of ANP release and positive inotropism, whereas the antagonists for salmon or amylin did not. Therefore, we suggest that rat alpha-CGRP causes a suppression of ANP release with positive inotropism through the receptor for CGRP(1) but not that for calcitonin and amylin.