Direct inhibitory effect of calcitonin gene-related peptide and atrial natriuretic peptide on gastric smooth muscle cells via different mechanisms.

Smooth muscle cells isolated from the gastric muscle layers of the guinea pig were used to determine whether calcitonin gene-related peptide (CGRP) and atrial natriuretic peptide (ANP) can inhibit the contractile response produced by 10(-6) M carbachol by exerting a direct action on muscle cells. In addition, the inhibitory effect of 2', 5'-dideoxyadenosine, an inhibitor of adenylate cyclase, on the CGRP-induced or ANP-induced relaxation of gastric smooth muscle cells were examined. CGRP and ANP inhibited the contractile response produced by carbachol in a dose-dependent manner, and the values of IC50 were 3 nM and 2 nM, respectively. 2',5'-dideoxyadenosine significantly inhibited the relaxation produced by CGRP. On the other hand, 2',5'-dideoxyadenosine did not have any significant effect on the relaxation produced by ANP. These results demonstrate the difference between intracellular mechanism responsible for gastric smooth muscle relaxation by CGRP and the mechanism responsible for muscle relaxation by ANP, and strongly suggest that the action of CGRP is mediated by adenosine 3',5'-cyclic monophosphate.