Amobi N, Guillebaud J, Coker C, Mulvin D, Smith I C
Biomedical Sciences Division, King's College London, UK.
Eur J Pharmacol. 1999 Feb 19;367(2-3):291-8. doi: 10.1016/s0014-2999(98)00989-3.
The alpha1-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 (pD2; 5.6 and 5.5 respectively). The contractions in longitudinal and circular muscle respectively were inhibited by prazosin (pA2, 8.6 and pKB, 9.2), 5-methylurapidil (pKB, 8.7 and 9.1) and less potently by spiperone (pA2, 7.1) or BMY 7378 (pKB, 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 alpha1-adrenoceptors with pharmacological profile of the alpha1A-subtype. However the involvement of alpha1A-adrenoceptor variants, such as the hypothesised alpha1L-subtype may underlie the differential effects of phenoxybenzamine in longitudinal and circular muscle. Factors contributing to chloroethylclonidine-sensitivity are discussed.
利用竞争性拮抗剂研究了介导人附睾输精管纵行肌和环行肌对去甲肾上腺素收缩反应的α1-肾上腺素能受体亚型。还研究了烷基化剂酚苄明和氯乙可乐定的作用。去甲肾上腺素引起纵行肌和环行肌浓度依赖性收缩，效力相当（pD2分别为5.6和5.5）。纵行肌和环行肌的收缩分别被哌唑嗪（pA2为8.6，pKB为9.2）、5-甲基尿嘧啶（pKB为8.7和9.1）抑制，而螺哌隆（pA2为7.1）或BMY 7378（pKB为6.3和6.6）的抑制作用较弱。环行肌而非纵行肌的收缩对酚苄明预处理相对不敏感。相反，氯乙可乐定预处理可降低两种肌型的收缩，并且增强纵行肌而非环行肌对酚苄明的敏感性。结果表明，人输精管两种肌型中去甲肾上腺素引起的收缩是通过具有α1A-亚型药理学特征的α1-肾上腺素能受体激活介导的。然而，α1A-肾上腺素能受体变体（如假设的α1L-亚型）的参与可能是酚苄明在纵行肌和环行肌中产生不同作用的基础。讨论了导致对氯乙可乐定敏感的因素。
