Rosskopf D
Institut für Pharmakologie, Universitätsklinikum Essen, Germany.
J Thromb Thrombolysis. 1999 Jul;8(1):15-24. doi: 10.1023/a:1008986329267.
On stimulation of platelets with agonists, for example, thrombin, a rapid rise in intracellular pH is observed. This alkalinization is mediated by an increase in transport activity of the Na(+)/H(+) exchanger isoform NHE1. In addition to this Na(+)/H(+) exchange mechanism, platelets express bicarbonate/chloride exchangers, which also contribute to pH(i) homeostasis. The main functions of NHE1 in platelets include pH(i) control, volume regulation, and participation in cell signaling. The isoform NHE1 is highly sensitive toward inhibition by EIPA, Hoe694, and Hoe642. The regulation of NHE1 activity is complex and is not completely understood. It includes the MAP kinase cascade, the Ca/calmodulin system, several heterotrimeric G proteins (Galpha12, Galpha13, Galphaq, and Galphai), small G proteins (ras, cdc42, rhoA), and downstream kinases (e.g., p160ROCK). Volume challenges stimulate tyrosine phosphorylation of cytoplasmic proteins, which ultimately activate NHE1. Thrombin, thromboxane, platelet-activating factor, angiotensin II, endothelin, phorbol ester, and Ca(2+) ionophors stimulate NHE1 activity in platelets. Blockade of platelet NHE1 can inhibit platelet activation. With the development of highly specific NHE1 inhibitors, detailed investigation of the relationships between NHE1 activity and platelet activation now becomes feasible.
在用激动剂（例如凝血酶）刺激血小板时，可观察到细胞内pH值迅速升高。这种碱化是由Na(+)/H(+)交换体异构体NHE1的转运活性增加介导的。除了这种Na(+)/H(+)交换机制外，血小板还表达碳酸氢根/氯离子交换体，这也有助于细胞内pH值（pH(i)）的稳态。NHE1在血小板中的主要功能包括控制pH(i)、调节体积以及参与细胞信号传导。异构体NHE1对EIPA、Hoe694和Hoe642的抑制高度敏感。NHE1活性的调节很复杂，尚未完全了解。它包括丝裂原活化蛋白激酶（MAP）级联反应、钙/钙调蛋白系统、几种异源三聚体G蛋白（Galpha12、Galpha13、Galphaq和Galphai）、小G蛋白（ras、cdc42、rhoA）以及下游激酶（例如p160ROCK）。体积变化刺激细胞质蛋白的酪氨酸磷酸化，最终激活NHE1。凝血酶、血栓素、血小板活化因子、血管紧张素II、内皮素、佛波酯和Ca(2+)离子载体可刺激血小板中的NHE1活性。阻断血小板NHE1可抑制血小板活化。随着高度特异性NHE1抑制剂的开发，现在对NHE1活性与血小板活化之间关系的详细研究变得可行。
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