Effect of calcitonin gene-related peptide on the neuroeffector mechanism of sympathetic nerve terminals in rat vas deferens

Abstract

In order to evaluate the mode of action of calcitonin gene-related peptide (CGRP) on the neuroeffector mechanism of peripheral sympathetic nerve fibers, the effects of CGRP were tested on the electrical stimulated and the non-stimulated preparations of the isolated rat vas deferens. The contractile responses, which were mediated predominantly by activation of postganglionic noradrenergic nerve fibers, were dose-dependently inhibited by CGRP in concentrations ranging from 0.1 to 10 nM. The inhibitory response produced by CGRP in high concentrations ( >2 nM ) usually returned to the control level at 20–30 min and were rarely tachyphylactic. The inhibitory action of CGRP was not modified by pretreatment with 10 −7 M propranolol or 10 −7 M atropine. Contractions produced by exogenous norepinephrine (NE) and 5-hydroxytryptamine (5-HT) in unstimulated preparations were not affected by pretreatment with CGRP in a low concentration ( <2 nM ). On the other hand, the contractions were slightly reduced 1 min after pretreatment with CGRP in high concentrations ( >5 nM ), which recovered in 15 min after constant flow washout. High concentrations of CGRP also caused a concentration-dependent relaxation on the precontracted preparations produced by high potassium (60 mM K +) solution. These results suggest that (1) CGRP in high concentrations ( >5 nM ) may have a non-specific inhibitory action on the postsynaptic plasma membrane of the smooth muscle cell and (2) a postulated CGRP receptor exists presynaptically in the rat vas deferens and that CGRP may inhibit the release of NE during adrenergic nerve stimulation.