吡考他胺对血小板血栓素A2受体结合的竞争性抑制作用。

Competitive inhibition of platelet thromboxane A2 receptor binding by picotamide.

作者信息

Modesti P A, Colella A, Abbate R, Gensini G, Neri Serneri G

机构信息

Clinica Medica I, University of Florence, Italy.

出版信息

Eur J Pharmacol. 1989 Oct 4;169(1):85-93. doi: 10.1016/0014-2999(89)90820-0.

DOI:10.1016/0014-2999(89)90820-0

PMID:2532145

Abstract

On the basis of indirect pharmacological evidence, picotamide, a methoxy derivative of 4-hydroxy-isophthalic acid (N,N'bis(3-picolyl)-4-methoxy-isophthalamide) has been postulated to inhibit platelet aggregation by competitively interfering with the thromboxane A2 (TxA2) platelet receptor. In the present study the interaction between picotamide and TxA2 receptors on human platelets was investigated by a direct radioligand assay method with [125I]PTA-OH and [3H]U46619 as labelled radioligands. The ONO11120 and U46619 inhibitory constants (Ki) for [125I]PTA-OH binding were 19 +/- 4 and 17 +/- 3 nM, respectively. Picotamide displaced [125I]PTA-OH binding with a Ki of 1472 +/- 321 nM. The Ki for ONO 11120 and U46619 on [3H]U46619 binding were 42 +/- 12 and 16 +/- 5 nM, respectively, whereas the Ki for picotamide was 1648 +/- 431 nM. These data provide evidence that picotamide can directly inhibit the TxA2 platelet receptor.

摘要

基于间接药理学证据，已推测4-羟基间苯二甲酸的甲氧基衍生物匹可托胺（N,N'-双(3-吡啶甲基)-4-甲氧基间苯二甲酰胺）通过竞争性干扰血栓素A2（TxA2）血小板受体来抑制血小板聚集。在本研究中，采用以[125I]PTA-OH和[3H]U46619作为标记放射性配体的直接放射性配体测定法，研究了匹可托胺与人血小板上TxA2受体之间的相互作用。[125I]PTA-OH结合的ONO11120和U46619抑制常数（Ki）分别为19±4和17±3 nM。匹可托胺以1472±321 nM的Ki取代[125I]PTA-OH结合。[3H]U46619结合上ONO 11120和U46619的Ki分别为42±12和16±5 nM，而匹可托胺的Ki为1648±431 nM。这些数据提供了证据，表明匹可托胺可直接抑制TxA2血小板受体。