萘哌地尔对α_1亚型受体的作用研究

Selective effects of Naftopidil on alpha1-adrenoreceptor subtype

目的研究萘哌地尔(naftopidil)对α1受体亚型的选择性作用。方法大鼠胸主动脉、脾、输精管分别富含了α1D、α1B、α1A3种亚型受体,分别制备这3种离体组织,在存在和不存在萘哌地尔时,按浓度累积法加入去甲肾上腺素(noradrenaline,NA),至组织达到最大收缩效应,得到相应的量效曲线,通过Schild法计算拮抗参数pA2值。结果萘哌地尔对主动脉、脾、输精管的拮抗参数pA2值分别为7.93(±0.13)、6.75(±0.01)、7.48(±0.30),其对α1D-AR的选择性是对α1B-AR的15.1倍,是对α1A-AR的2.8倍。结论萘哌地尔为一种高选择性的α1A/1D亚型拮抗剂。

Aim To investigate the selective effect of Naftopidil on three alphal-adrenoreceptor （ α1 -adrenoceptor） subtypes. Methods The α1-adrenoceptors of rat aortic artery, spleen, and vas deferens were respectively rich in α1D-adrenoceptor subtype, α1B-adrenoceptor subtype, and α1A-adrenoceptor subtype. The three above-mentioned tissues were isolated, in the absence and presence of Naftopidil, the tissues were then contracted with NA administered by concentration cumulatively increments respectively. Estimates of affinity were represented as the apparent pA2 values, calculated by Schild methods. Results The pA2 values of Naftopidil for the aortic artery, spleen and vas deferens were7.93 （±0.13）, 6.75（±0.01）, 7.48（ ±0. 30）, respectively. Naftopidil was selective for the α1D-adrenoeeptor with approximately 15. 1 and 2.8 fold higher affinity than for the Otis-and α1A-adrenoeeptor subtypes, respectively. Conclusion The suggested results show that Naftopidil is a selective α1A/iD-adrenoreceptor antagonist.