猫脑动脉中收缩介导前列腺素受体的进一步特征研究。血栓素受体拮抗剂AH 23848的作用

Further characterization of the contraction-mediating prostanoid receptors in feline cerebral arteries. Effects of the thromboxane-receptor antagonist AH 23848.

作者信息

Uski T K

机构信息

Department of Clinical Pharmacology, Lund University Hospital, Sweden.

出版信息

Acta Physiol Scand. 1988 Aug;133(4):519-24. doi: 10.1111/j.1748-1716.1988.tb08436.x.

DOI:10.1111/j.1748-1716.1988.tb08436.x

PMID:2976236

Abstract

The effects of the thromboxane-receptor antagonist AH 23848 were investigated on isolated feline basilar arteries (BA). AH 23848 (10(-6) mol l-1) had no effect on contractions induced by 5-hydroxytryptamine or potassium, whereas the drug (10(-8)-10(-6) mol l-1) induced a parallel shift to the right in contractions induced by the thromboxane A2 mimic U46619. There was no depression of the maximum contraction, indicating competitive antagonism. The Schild plot revealed a slope index of unity with a pA2 value of 8.46. In contrast, 10(-6) mol l-1 AH 23848 depressed the maximum PGF2 alpha-induced contraction significantly from 100% to 13%. U46619 was able to induce a contraction amounting to 98% if the drug was added on top of the PGF2 alpha-induced contraction in the presence of 10(-6) mol l-1 AH 23848. The results provide strong support for previous suggestions that prostanoid-induced contractions in the feline BA are mediated by two receptor subtypes, one of which can be classified as a thromboxane-sensitive (TP) receptor.

摘要

研究了血栓素受体拮抗剂AH 23848对猫离体基底动脉（BA）的作用。AH 23848（10⁻⁶ mol·l⁻¹）对5-羟色胺或钾诱导的收缩无影响，而该药物（10⁻⁸ - 10⁻⁶ mol·l⁻¹）使血栓素A2类似物U46619诱导的收缩呈平行右移。最大收缩无降低，表明为竞争性拮抗作用。Schild图显示斜率指数为1，pA2值为8.46。相比之下，10⁻⁶ mol·l⁻¹的AH 23848使PGF2α诱导的最大收缩从100%显著降低至13%。在存在10⁻⁶ mol·l⁻¹ AH 23848的情况下，如果在PGF2α诱导的收缩基础上添加U46619，U46619能够诱导98%的收缩。这些结果为先前的观点提供了有力支持，即猫基底动脉中前列腺素诱导的收缩由两种受体亚型介导，其中一种可归类为血栓素敏感（TP）受体。