Effect of capsaicin on smooth muscles of rat vas deferens: involvement of calcitonin gene-related peptide?

The effect of capsaicin on the rat vas deferens was examined in relation to the role of endogenous calcitonin gene-related peptide (CGRP) in modifying the contractility of smooth muscles. Capsaicin attenuated the twitch response of the rat vas deferens induced by the transmural nerve stimulation (TNS) in vitro. The effect of capsaicin was transient and developed tachyphylaxis rapidly. Capsaicin inhibited the contraction induced by the direct electrical stimulation of the innervated tissues in the presence of tetrodotoxin but not of the surgically denervated tissues. CGRP-like immunoreactive nerves were demonstrated to be present in the rat vas deferens. Exogenously applied CGRP inhibited both the TNS-induced twitch response and the contraction induced by direct electrical stimulation. Both capsaicin and CGRP slightly hyperpolarized the resting membrane potential of smooth muscle cells but did not affect the amplitude of the excitatory junction potentials. The intensity of CGRP-like immunoreactivity was reduced markedly after the in vitro incubation of the tissue with capsaicin. No CGRP-like immunoreactive nerves were detected in the denervated tissues. Thus, capsaicin inhibited both the TNS-induced twitch response and the contraction induced by direct stimulation of the smooth muscles only when CGRP-like immunoreactive nerves were normally present. These results suggest that capsaicin releases endogenous CGRP and that the released CGRP inhibits the contraction of the rat vas deferens by acting directly on smooth muscle cells but not on the sympathetic nerves.