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 sympathetic twitch whose amplitude was transiently enhanced by the selective tachykinin NK1 receptor agonist, [Sar9,Met(O2)11]substance P (0.3-30 nM), but not by selective NK2 and NK3 receptor agonists. Potentiation by [Sar9,Met(O2)11]substance P was antagonized by (+/-)-CP 96,345 [(2S,3S)-cis-2-(diphenylmethyl)-N- [(2-methoxyphenyl)-methyl]-1-azabicyclo[2.2.2]octan-3-amine] (IC50 = 0.1 microM). On the other hand, electrical field stimulation-induced contractions were inhibited by calcitonin gene-related peptide, CGRP (0.1-30 nM), and this action was reduced by its antagonist, human CGRP-(8-37) (3 microM). [Sar9,Met(O2)11]substance P (3 nM) did not affect either high-K+ or noradrenaline-induced contraction, while CGRP (3 nM) significantly reduced the noradrenaline-induced motor response. Capsaicin (1 microM) inhibited sympathetic twitches, and this effect was partially antagonized by human CGRP-(8-37). In the presence of this antagonist, capsaicin induced a short-living and (+/-)-CP 96,345-sensitive twitch enhancement. These data suggest that the sympathetic control of mouse vas deferens motility can be modulated in an opposite manner by tachykinin NK1 (prejunctionally located) and by CGRP (pre- and/or postjunctionally located) receptors.