Differential inhibition in the human vas deferens by phenoxybenzamine: A possible mechanism for its contraceptive action

Abstract

The effect of phenoxybenzamine on in vitro contractile responses of human vasectomy tissues was investigated. Phenoxybenzamine (0.01-10 μmol l-1) produced a differential inhibition of contractions induced by noradrenaline (1-300 μmol l(-1)) in the human vas deferens in that it blocked the longitudinal but not the circular muscle. Contractions of both muscle types induced by noradrenaline (100 μmol l-1) were inhibited by either prazosin (0.01-10 μmol l-1, a competitive α1-selective adrenoceptor antagonist or benextramine (0.01-10 μmol l-1, an irreversible α1-adrenoceptor blocker, but were unaffected by chloroethylclonidine (0.1-100 μmol l-1), an irreversible α(1B)-adrenoceptor blocker. In calcium-free/EGTA (1 mmol l-1) medium, contractions of the longitudinal but not circular muscle induced by noradrenaline (100 μmol l-1) were inhibited by phenoxybenzamine (0.01-1 μmol l-1). Chloroethylclonidine (10-100 μmol l-1) was ineffective on both muscle types in calcium-free medium, but, on readmission of calcium, it markedly inhibited the recovery of longitudinal but not the circular muscle. These results suggest a mechanism for the male contraceptive action of phenoxybenzamine by a selective blockade of longitudinal but not circular muscle contractions. The results are discussed in relation to (i) the possible involvement of receptor reserves for noradrenaline and of α1-adrenoceptor subtypes coupled in the longitudinal and circular muscle to different mechanisms for increasing cytosolic calcium, (ii) a role in the longitudinal muscle for chloroethylclonidine-sensitive α1-adrenoceptors in replenishment of a functional pool of intracellular calcium and (iii) the inhibition of sperm emission by phenoxybenzamine.