Amobi N I, Smith I C
Biomedical Sciences Division, King's College, London, UK.
J Reprod Fertil. 1995 Mar;103(2):215-21. doi: 10.1530/jrf.0.1030215.
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.
研究了酚苄明对人体输精管结扎组织体外收缩反应的影响。酚苄明（0.01 - 10 μmol l⁻¹）对去甲肾上腺素（1 - 300 μmol l⁻¹）诱导的人体输精管收缩产生差异性抑制，即它阻断纵向肌但不阻断环形肌。去甲肾上腺素（100 μmol l⁻¹）诱导的两种肌型收缩，均可被竞争性α1选择性肾上腺素能受体拮抗剂哌唑嗪（0.01 - 10 μmol l⁻¹）或不可逆α1肾上腺素能受体阻滞剂苄环烷（0.01 - 10 μmol l⁻¹）抑制，但不受不可逆α1B肾上腺素能受体阻滞剂氯乙可乐定（0.1 - 100 μmol l⁻¹）影响。在无钙/EGTA（1 mmol l⁻¹）培养基中，酚苄明（0.01 - 1 μmol l⁻¹）抑制去甲肾上腺素（100 μmol l⁻¹）诱导的纵向肌而非环形肌收缩。氯乙可乐定（10 - 100 μmol l⁻¹）在无钙培养基中对两种肌型均无效，但重新加入钙后，它显著抑制纵向肌而非环形肌的恢复。这些结果提示了酚苄明男性避孕作用的一种机制，即选择性阻断纵向肌而非环形肌收缩。结合以下方面对结果进行了讨论：（i）去甲肾上腺素受体储备以及纵向肌和环形肌中与增加胞质钙的不同机制偶联的α1肾上腺素能受体亚型的可能参与；（ii）氯乙可乐定敏感的α1肾上腺素能受体在纵向肌中对补充细胞内钙功能池的作用；（iii）酚苄明对精子射出的抑制作用。
