Abstract

Calcitonin gene-related peptide (CGRP) inhibits the twitch response of the rat vas deferens induced by nerve stimulation. Inasmuch as CGRP-like immunoreactive nerves were demonstrated to be present in the rat vas deferens, the effect of CGRP on the contractile activity of the tissue was pharmacologically and electrophysiologically analyzed in vitro. The twitch response of the vas deferens induced by transmural nerve stimulation was inhibited by rat CGRP, porcine CGRP and human CGRP (hCGRP). Both ED50 values and the extent of the maximum inhibition of the twitch response were the same for these CGRP groups. hCGRP (10(-8) to 10(-7) M) hyperpolarized the resting membrane potential of smooth muscle cells but did not affect the amplitude of excitatory junction potentials induced by nerve stimulation. Neither the frequency of occurrence nor the amplitude of spontaneous junction potentials were affected by hCGRP. The threshold potentials for the generation of action potentials were less negative in the presence of hCGRP. hCGRP reduced slightly the contraction of the tissue induced by norepinephrine and by adenosine 5'-triphosphate. hCGRP reduced markedly the contractions induced by direct electrical stimulation of both denervated and normal tissues in the presence of tetrodotoxin. These results indicate that CGRP does not affect the release of a sympathetic neurotransmitter. CGRP appears to attenuate the contraction of the rat vas deferens through suppression of both the excitability and excitation-contraction coupling of the smooth muscle.