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

FEBS Letters

Gárdos, George³  Hunyady, László¹  Cragoe, Edward J.²  Sarkadi, Balázs³  Spät, András¹ 

[1] Department of Physiology, Semmelweis University of Medicine, Puskin u. 9, PO Box 259, H-1444 Budapest 8 Hungary;Merck Sharp & Dohme Research Laboratories, West Point, PA 19486, USA;National Institute of Haematology and Blood Transfusion, H-1113 Budapest, Hungary

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;   

DOI  :  10.1016/0014-5793(87)81133-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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.

【 授权许可】

Unknown