Activation of sodium‐proton exchange is not a prerequisite for Ca2+ mobilization and aggregation in human platelets

[摘要]

Recently it has been suggested [(1987) Nature 325, 456–458; (1987) FEBS Lett. 212, 123–126] that the activation of Na⁺/H⁺ exchange is a prerequisite for platelet aggregation and the development of the Ca²⁺ signal. As direct evidence for the role of the Na⁺/H⁺-exchange pathway the inhibition of the Ca²⁺ signal by EIPA, a specific inhibitor of Na⁺/H⁺ exchange, was offered. Here we demonstrate that low concentrations of EIPA (below 1 μM) completely block Na⁺/H⁺ exchange while EIPA inhibits aggregation or Ca²⁺ mobilization only in concentrations 100-times greater than 1 μM. Moreover, another amiloride analogue, CBDMB, developed to act predominantly on Na⁺/Ca²⁺ exchange, does not affect Na⁺/H⁺ exchange in platelets but blocks aggregation and Ca²⁺ mobilization. We conclude that while Na⁺/H⁺ exchange has a fundamental role in platelet functions it is not prerequisite for the development of Ca²⁺ signal and aggregation.

[学科分类] 生物化学/生物物理

[关键词] Ca2+ signal;Na+/H+ exchange;Thrombin;Amiloride analogue;(Human platelet);[Ca2+]i;cytoplasmic free Ca2+ concentration;CBDMB;5-(N-4-chlorobenzyl)-N-(2′;4′-dimethyl)benzamil;DMB;N-(2′;4′-dimethyl)benzamil;EIPA;5-(N-ethyl-N-isopropyl)amiloride;InsP3;inositol 1;4;5-trisphosphate;DAG;1;2-diacylglycerol