Calcitonin gene-related peptides relax guinea pig and rat gastric smooth muscle

Rat and human α- and β-calcitonin gene-related peptide (CGRP), in the concentration range 1-100 nM, produced sustained relaxations of longitudinal muscle from the rat fundus and guinea pig gastric corpus. The peptides were equipotent and equally effective. Tetrodotoxin, adrenoceptor and purine receptor antagonists, somatostatin, apamin and Tyr-rat α-CGRP-(28-37) peptide did not modify the action of the CGRP peptides. The CGRP-induced responses were inhibited by verapamil and potentiated by Bay K-8644. Incubation of the tissues with indomethacin markedly reduced the magnitude of the CGRP- and adrenaline-induced relaxations, but their responsiveness was restored by addition of prostaglandins E₁, E₂ and E_2α in concentrations that alone did not affect the motility of the indomethacin-treated strips. It is suggested that an inhibitory receptor for CGRP on gastric smooth muscle cells is linked to calcium channels and may be activated or sensitized by endogenous prostaglandins.