INVOLVEMENT OF ATP-SENSITIVE K-GENE-RELATED PEPTIDE ON NEUROTRANSMISSION IN RAT VAS-DEFERENS( CHANNELS IN THE INHIBITORY EFFECT OF CALCITONIN)

This study investigated the inhibitory action of human calcitonin-gene -related peptide (CGRP) on neurotransmission in rat isolated vas defer ens. The electrically stimulated contractile responses, which were med iated predominantly by activation of postganglionic noradrenergic nerv e fibers, were concentration-dependently inhibited by human CGRP (0.1- 100 nM, IC50 = 2.15 +/- 0.21 nM, n = 17). Human CGRP at concentrations greater than 3 nM reduced the contractile responses to exogenous nora drenaline and ATP. The inhibitory effect of human CGRP on the electric ally stimulated or agonist-induced contractions was antagonized by hum an CGRP-(8-37), the CGRP receptor antagonist. Glibenclamide (3-10 mu M ) 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 CGRT at low concentrations exerts its inhibitory action mainly by acting on CGRP receptors at the sympathetic nerve terminals supplyi ng rat vas deferens and the activation of ATP-sensitive KC channels is at least in part involved in the action of human CGRP on neurotransmi ssion.