Involvement of ATP-sensitive K + channels in the inhibitory effect of calcitonin gene-related peptide on neurotransmission in rat vas deferens

Abstract

This study investigated the inhibitory action of human calcitonin-gene-related peptide (CGRP) on neurotransmission in rat isolated vas deferens. The electrically stimulated contractile responses, which were mediated predominantly by activation of postganglionic noradrenergic nerve fibers, were concentration-dependently inhibited by human CGRP (0.1–100 nM, IC 50=2.15±0.21 nM, n=17). Human CGRP at concentrations greater than 3 nM reduced the contractile responses to exogenous noradrenaline and ATP. The inhibitory effect of human CGRP on the electrically stimulated or agonist-induced contractions was antagonized by human CGRP-(8–37), the CGRP receptor antagonist. Glibenclamide (3–10 μM) decreased the effect of human CGRP at a concentration greater than 1 nM whilst glibenclamide did not affect the inhibitory effect of human CGRP on the agonist-induced contractions. These results indicate that human CGRP at low concentrations exerts its inhibitory action mainly by acting on CGRP receptors at the sympathetic nerve terminals supplying rat vas deferens and the activation of ATP-sensitive K + channels is at least in part involved in the action of human CGRP on neurotransmission.