匹可托胺对人血小板中钙动员和磷脂酶C激活的影响。

Effect of picotamide on the calcium mobilization and phospholipase C activation in human platelets.

作者信息

Pulcinelli F M, Pignatelli P, Riondino S, Parisi S, Castiglioni C, Gazzaniga P P

机构信息

Dept. of Experimental Medicine, University of Rome La Sapienza, Italy.

出版信息

Thromb Res. 1994 Jun 1;74(5):453-61. doi: 10.1016/0049-3848(94)90266-6.

DOI:10.1016/0049-3848(94)90266-6

PMID:8085246

Abstract

The effect of picotamide (G137 or N,N'-bis-3-picolyl-4-methoxyisophthalamide), a dual thromboxane A2 (TxA2) synthetase inhibitor/TxA2 endoperoxide receptor antagonist, on the phospholipase C (PLC) activation and calcium mobilization in human platelets stimulated by arachidonic acid (AA) and TxA2 receptor synthetic agonist U46619, has been studied. Preincubation with picotamide (10(-4) M) for 1 and 3 min significantly reduced (p < 0.03 and p < 0.005 respectively) the calcium concentration changes induced in gel-filtered platelets (GFPs) by U46619 125 nM and 250 nM. Picotamide also reduced the calcium concentration changes induced in GFPs by AA 75 and 150 microM and by ADP 5 and 10 microM. In thrombin degranulated platelets picotamide inhibited the effect of U46619 up to 500 nM. The PLC activation, as indicated by inositol-1,3,4 P3 (Ins 1,3,4 P3) formation in response to U46619 250 nM and AA 150 microM was also inhibited by picotamide. These results may suggest a dual effect of picotamide on the receptor/effector systems through which TxA2 mediates platelet activation.

摘要

已研究了双重血栓素A2（TxA2）合成酶抑制剂/ TxA2内过氧化物受体拮抗剂匹可他胺（G137或N，N'-双-3-吡啶甲基-4-甲氧基间苯二甲酰胺）对花生四烯酸（AA）和TxA2受体合成激动剂U46619刺激的人血小板中磷脂酶C（PLC）激活和钙动员的影响。用匹可他胺（10^(-4) M）预孵育1分钟和3分钟可分别显著降低（p <0.03和p <0.005）125 nM和250 nM的U46619在凝胶过滤血小板（GFP）中诱导的钙浓度变化。匹可他胺还降低了75和150 microM的AA以及5和10 microM的ADP在GFP中诱导的钙浓度变化。在凝血酶脱颗粒的血小板中，匹可他胺可抑制高达500 nM的U46619的作用。由250 nM的U46619和150 microM的AA引起的肌醇-1,3,4-三磷酸（Ins 1,3,4 P3）形成所表明的PLC激活也受到匹可他胺的抑制。这些结果可能表明匹可他胺对TxA2介导血小板激活的受体/效应系统具有双重作用。