Functional characterization of alpha(1)-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 s tudied using competitive antagonists. The effects of the alkylating agents, phenoxybenzamine and chloroethylclonidine were also investigated. Noradren aline evoked concentration-dependent contractions of longitudinal and circu lar muscle with comparable potencies (pD(2); 5.6 and 5.5 respectively). The contractions in longitudinal and circular muscle respectively were inhibit ed by prazosin (pA(2), 8.6 and pK(B), 9.2), 5-methylurapidil (pK(B), 8.7 an d 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 comp aratively insensitive to pretreatment with phenoxybenzamine. In contrast pr etreatment with chloroethylclonidine reduced the contractions in both muscl e types and also enhanced phenoxybenzamine-sensitivity in longitudinal but not circular muscle. The results suggest that contractions evoked by noradr enaline in both muscle types of human vas deferens is mediated via activati on of alpha(1)-adrenoceptors with pharmacological profile of the alpha(1A)- subtype. However the involvement of alpha(1A)-adrenoceptor variants, such a s the hypothesised alpha(1L)-subtype may underlie the differential effects of phenoxybenzamine in longitudinal and circular muscle. Factors contributi ng to chloroethylclonidine-sensitivity are discussed. (C) 1999 Elsevier Sci ence B.V. All rights reserved.