贝尼司明作为U46619介导的大鼠小肠系膜动脉收缩的不可逆非竞争性拮抗剂。

Benextramine acts as an irreversible noncompetitive antagonist of U46619-mediated contraction of the rat small mesenteric artery.

作者信息

Van der Graaf P H, Stam W B, Saxena P R

机构信息

Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, Netherlands.

出版信息

Eur J Pharmacol. 1996 Apr 11;300(3):211-4. doi: 10.1016/0014-2999(96)00040-4.

DOI:10.1016/0014-2999(96)00040-4

PMID:8739210

Abstract

We have studied the effects of benextramine on the U46619 (11 alpha,9 alpha-epoxymethano-15S-hydroxy-prosta-5Z,13E-dienoic acid)-mediated contraction of the rat isolated small mesenteric artery. U46619 (10 nM-10 microM) produced a concentration-dependent contraction of the small mesenteric artery. The selective prostanoid TP receptor antagonist, SQ 30,741 ([1S-[1 alpha,2 alpha(5Z),3 alpha,4 alpha]]-7- [[[[[(oxaheptyl)amino]acetyl]amino]-methyl]-7-oxabicyclo[2.2.1]hep t-2-yl]-5- heptenoic acid; 1 microM), produced a parallel, rightward shift of the U46619 curve with an associated pA2 value of 7.43 +/- 0.09. Treatment of tissues with 100 microM benextramine depressed the maximum response to U46619 in a time-dependent manner. However, neither SQ 30,741 (10 microM) nor U46619 (10 microM) incubation significantly protected against this effect. Thus, benextramine acts as an irreversible noncompetitive antagonist of U46619. The mechanism of this action is not yet clear.

摘要

我们研究了苯苄胺对U46619（11α，9α-环氧甲叉-15S-羟基-前列腺-5Z，13E-二烯酸）介导的大鼠离体小肠系膜动脉收缩的影响。U46619（10 nM - 10 μM）可引起小肠系膜动脉浓度依赖性收缩。选择性前列腺素TP受体拮抗剂SQ 30741（[1S-[1α，2α(5Z)，3α，4α]]-7-[[[[(氧杂庚基)氨基]乙酰基]氨基]-甲基]-7-氧杂双环[2.2.1]庚-2-基]-5-庚烯酸；1 μM）使U46619曲线平行右移，相关的pA2值为7.43±0.09。用100 μM苯苄胺处理组织会以时间依赖性方式降低对U46619的最大反应。然而，孵育10 μM的SQ 30741或10 μM的U46619均不能显著预防这种效应。因此，苯苄胺作为U46619的不可逆非竞争性拮抗剂起作用。这种作用机制尚不清楚。