Functional characterization of α1-adrenoceptor subtypes in longitudinal and circular muscle of human vas deferens

The alpha(1)-adrenoceptor subtype(s) mediating contraction to noradrenaline in longitudinal and circular muscle of human epididymal vas deferens was studied using competitive antagonists. The effects of the alkylating agents, phenoxybenzamine and chloroethylclonidine were also investigated. Noradrenaline evoked concentration-dependent contractions of longitudinal and circular muscle with comparable potencies (pD(2); 5.6 and 5.5 respectively). The contractions in longitudinal and circular muscle respectively were inhibited by prazosin (pA(2), 8.6 and pK(B), 9.2), 5-methylurapidil (pK(B), 8.7 and 9.1) and less potently by spiperone (pA(2), 7.1) or BMY 7378 (pK(B), 6.3 and 6.6). Contractions of the circular but not longitudinal muscle was comparatively insensitive to pretreatment with phenoxybenzamine. In contrast pretreatment with chloroethylclonidine reduced the contractions in both muscle types and also enhanced phenoxybenzamine-sensitivity in longitudinal but not circular muscle. The results suggest that contractions evoked by noradrenaline in both muscle types of human vas deferens is mediated via activation of alpha(1)-adrenoceptors with pharmacological profile of the alpha(1A)-subtype. However the involvement of alpha(1A)-adrenoceptor variants, such as the hypothesised alpha(1L)-subtype may underlie the differential effects of phenoxybenzamine in longitudinal and circular muscle. Factors contributing to chloroethylclonidine-sensitivity are discussed. (C) 1999 Elsevier Science B.V. All rights reserved.