一项关于前列环素类似物的研究区分了神经元型和中性粒细胞型 IP 受体。

A study of prostacyclin mimetics distinguishes neuronal from neutrophil IP receptors.

作者信息

Wise H, Qian Y M, Jones R L

机构信息

Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T.

出版信息

Eur J Pharmacol. 1995 May 24;278(3):265-9. doi: 10.1016/0014-2999(95)00173-i.

DOI:10.1016/0014-2999(95)00173-i

PMID:7589166

Abstract

The prostacyclin mimetics BMY 45778 (3-[4-(4,5-diphenyl-2-oxazolyl)-5-oxazolyl]phenoxy]acetic acid), BMY 42393 (2-[3-[2-(4,5-diphenyl-2-oxazolyl)ethyl]phenoxy]acetic acid) and EP 185 (rac 5-endo-(6'-carboxyhex-2'Z-enyl)-6-exo-(p-methoxyphenyl- phenyl-methylazino)-bicyclo[2.2.2]oct-2-ene) inhibited rat neutrophil aggregation stimulated by N-formyl-methionyl-leucyl-phenylalanine (IC50 = 20, 462, and 1195 nM respectively). In contrast only BMY 45778 (1-10 microM) produced any significant inhibition (10-20%) of the spontaneous activity of rat colon. BMY 45778 (10 microM) also attenuated the inhibitory effect of the prostacyclin analogue cicaprost on rat colon, whereas BMY 42393 and EP 185 did not. BMY 45778 appears to be a low affinity partial agonist at prostacyclin receptors on rat colon and its low potency in rat colon compared with rat neutrophils suggests the presence of a different prostacyclin receptor located on enteric neurones.

摘要

前列环素类似物BMY 45778（3-[4-(4,5-二苯基-2-恶唑基)-5-恶唑基]苯氧基]乙酸）、BMY 42393（2-[3-[2-(4,5-二苯基-2-恶唑基)乙基]苯氧基]乙酸）和EP 185（外消旋5-内-(6'-羧基己-2'Z-烯基)-6-外-(对甲氧基苯基-苯基-甲基叠氮基)-双环[2.2.2]辛-2-烯）抑制了由N-甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸刺激的大鼠中性粒细胞聚集（IC50分别为20、462和1195 nM）。相比之下，只有BMY 45778（1 - 10 microM）对大鼠结肠的自发活性产生了任何显著抑制（10 - 20%）。BMY 45778（10 microM）也减弱了前列环素类似物西卡前列素对大鼠结肠的抑制作用，而BMY 42393和EP 185则没有。BMY 45778似乎是大鼠结肠前列环素受体的低亲和力部分激动剂，与大鼠中性粒细胞相比，它在大鼠结肠中的效力较低，这表明在肠神经元上存在一种不同的前列环素受体。