Thromboxane A2 and prostaglandin endoperoxide receptors in platelets and vascular smooth muscle.
Thromboxane A2 and prostaglandin endoperoxide receptors in platelets and vascular smooth muscle.
复制标题
血小板和血管平滑肌中的血栓素 A2 和前列腺素内过氧化物受体。
DOI：
10.1161/01.cir.72.6.1202
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发表时间：
1985
期刊：
影响因子：
37.8
通讯作者：
Halushka,PV
中科院分区：
文献类型：
--
作者：
SaussyJr,DL;Mais,DE;Knapp,DR;Halushka,PV
新合成的血栓烷(TX)A2/前列腺素(PG)H2受体拮抗剂PTA14-二氢-13-氮杂-15α-β-欧米伽-四氮杂-血栓素A2(9，11-Dimethylmethano-11，12-methano-16-(3-iodo-4-hydroxyphenyl)-13，-OH)是一种竞争性拮抗剂，能拮抗稳定的过氧化产物类似物U46619诱导的人血小板聚集。这种拮抗作用是由于竞争性阻断血小板TXA2/PGH2受体，因为i-PTA-OH不拮抗ADP诱导的不依赖TXA2/PGH2的聚集的第一阶段，也不抑制TXA2的合成。此外，对U46619(0.1至40微米)的剂量-反应曲线的分析表明，I-PTA-OH在浓度增加(0.5-10微米)时使剂量-反应曲线平行右移。进一步分析斯柴尔德曲线形式的数据，得到一条斜率(m=1.03)与-1没有显著差异的直线。这些结果与I-PTA-OH作为TXA2/PGH2受体的竞争性拮抗剂的观点是一致的。
9,11-Dimethylmethano-11,12-methano-16-(3-iodo-4-hydroxyphenyl)-13, 14-dihydro-13-aza-15 alpha beta-omega-tetranor-TXA2 (I-PTA-OH), a recently synthesized thromboxane (TX) A2/prostaglandin (PG) H2 receptor antagonist, was shown to be a competitive antagonist of human platelet aggregation induced by the stable endoperoxide analog U46619. This antagonism was due to competitive blockade of the platelet TXA2/PGH2 receptor since I-PTA-OH did not antagonize the first phase of ADP-induced aggregation which is TXA2/PGH2 independent, nor did it inhibit TXA2 synthesis. In addition, analysis of dose-response curves to U46619 (0.1 to 40 microM) in the presence of increasing concentrations of I-PTA-OH (0.5 to 10 microM) showed that I-PTA-OH produced a parallel rightward shift of the dose-response curve. Further analysis of the data in the form of a Schild plot yielded a straight line with a slope (m = 1.03) not significantly different from -1. These results are consistent with the notion that I-PTA-OH acts as a competitive antagonist of the TXA2/PGH2 receptor.