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用α,β-亚甲基三磷酸腺苷选择性激活P2X1嘌呤受体引起的血小板形状改变

Platelet shape change evoked by selective activation of P2X1 purinoceptors with alpha,beta-methylene ATP.

作者信息

Rolf M G, Brearley C A, Mahaut-Smith M P

机构信息

Department of Physiology, University of Cambridge, UK.

出版信息

Thromb Haemost. 2001 Feb;85(2):303-8.

Abstract

Simultaneous measurements of [Ca2+]i and light transmission were used to examine the relationship between P2X1 receptor activation and functional platelet responses. The P2X1 agonist alpha,beta-MeATP evoked a transient [Ca2+]i increase and a reversible decrease in light transmission; both responses required external Ca2+ and the nucleotidase apyrase. The transmission response was due to shape change only, verified by scanning electron microscopy and insensitivity to Reopro, a GPIIbIIIa antagonist. Alpha,beta-MeATP stimulated smaller shape changes than ADP, however P2X1 responses had a lifespan of <2 h following resuspension in saline and may be considerably larger in vivo. A peak [Ca2+]i increase of >50 nM was required for detectable shape change. Overlap of concentration-response relationships for alpha,beta-MeATP-evoked [Ca2+]i and shape change suggests that other second messengers are not involved. Therefore, the physiological P2X1 agonist ATP can contribute to platelet activation, in contrast to its previously described inhibitory action at metabotropic platelet purinoceptors.

摘要

同时测量细胞内钙离子浓度([Ca2+]i)和光透射率,以研究P2X1受体激活与血小板功能反应之间的关系。P2X1激动剂α,β-甲基ATP(alpha,beta-MeATP)可引起细胞内钙离子浓度的短暂升高以及光透射率的可逆降低;这两种反应均需要细胞外钙离子和核苷酸酶(外切核苷酸酶)。透射反应仅由形状变化引起,通过扫描电子显微镜和对糖蛋白IIbIIIa拮抗剂Reopro不敏感得以证实。然而,与二磷酸腺苷(ADP)相比,α,β-甲基ATP刺激的形状变化较小,不过P2X1反应在重悬于盐溶液后持续时间小于2小时,在体内可能会大得多。可检测到的形状变化需要细胞内钙离子浓度峰值升高超过50 nM。α,β-甲基ATP引起的细胞内钙离子浓度升高和形状变化的浓度-反应关系重叠表明,其他第二信使不参与其中。因此,与之前描述的其对代谢型血小板嘌呤受体的抑制作用相反,生理状态下的P2X1激动剂三磷酸腺苷(ATP)可促进血小板激活。

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