OPPOSITE MODULATION BY TACHYKININ (NK1) AND CGRP RECEPTORS OF SYMPATHETIC CONTROL OF MOUSE VAS-DEFERENS MOTILITY

Electrical field stimulation of isolated mouse vas deferens elicited s ympathetic twitch whose amplitude was transiently enhanced by the sele ctive tachykinin NK1 receptor agonist, [Sar(9),Met(O-2)(11)]substance P (0.3-30 nM), but not by selective NK2 and NK3 receptor agonists. Pot entiation by [Sar(9),Met(O-2)(11)]substance P was antagonized by(+/-)- CP 96,345 xyphenyl-)methyl]1-azabicyclo[2,2,2]octan-3-amine] (IC50 = 0 .1 mu M). On the other hand, electrical field stimulation-induced cont ractions were inhibited by calcitonin gene-related peptide, CGRP (0.1- 30 nM), and this action was reduced by its antagonist, human CGRP-(8-3 7) (3 mu M). [Sar(9),Met(O-2)(11)]substance P (3 nM) did not affect ei ther high-K+ or noradrenaline-induced contraction, while CGRP (3 nM) s ignificantly reduced the noradrenaline-induced motor response. Capsaic in (1 mu M) inhibited sympathetic twitches, and this effect was partia lly antagonized by human CGRP-(8-37). In the presence of this antagoni st, capsaicin induced a short-living and (+/-)-CP 96,345-sensitive twi tch enhancement. These data suggest that the sympathetic control of mo use vas deferens motility can be modulated in an opposite manner by ta chykinin NK, (prejunctionally located) and by CGRP (pre- and/or postju nctionally located) receptors.