Differential inhibition in the human vas deferens by phenoxybenzamine: a possible mechanism for its contraceptive action.
The effect of phenoxybenzamine on in vitro contractile responses of human vasectomy tissues was investigated. Phenoxybenzamine (0.01-10 mumol l-1) produced a differential inhibition of contractions induced by noradrenaline (1-300 mumol 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 mumol l-1) were inhibited by either prazosin (0.01-10 mumol l-1), a competitive alpha 1-selective adrenoceptor antagonist or benextramine (0.01-10 mumol l-1), an irreversible alpha 1-adrenoceptor blocker, but were unaffected by chloroethylclonidine (0.1-100 mumol l-1), an irreversible alpha 1B-adrenoceptor blocker. In calcium-free/EGTA (1 mmol l-1) medium, contractions of the longitudinal but not circular muscle induced by noradrenaline (100 mumol l-1) were inhibited by phenoxybenzamine (0.01-1 mumol l-1). Chloroethylclonidine (10-100 mumol l-1) was ineffective on both muscle types in calcium-free medium, but, on readmission of calcium, in 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 alpha 1-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 alpha 1-adrenoceptors in replenishment of a functional pool of intracellular calcium and (iii) the inhibition of sperm emission by phenoxybenzamine.
Amobi
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Biomedical Sciences Division, King's College, London, UK.
Smith
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003272:Contraceptive Agents, Male; D003538:Cystamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D003272:Contraceptive Agents, Male; D010643:Phenoxybenzamine; C051731:chlorethylclonidine; C029998:benextramine; D003000:Clonidine; D003538:Cystamine; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin