Inhibition of Na+/H+ exchange reduces Ca2+ mobilization without affecting the initial cleavage of phosphatidylinositol 4,5‐bisphosphate in thrombin‐stimulated platelets

FEBS Letters

Scheid, P.¹  Gorter, G.¹  Akkerman, J.W.N.¹  Siffert, G.¹  Siffert, W.¹  Riemens, T.¹ 

[1] Institut für Physiologie, Ruhr-Universität, 4630 Bochum, FRG and Department of Haematology, University Hospital, NL-3511 GV Utrecht, The Netherlands

关键词: Na+/H+ exchange;    Amiloride;    Phosphoinositide;    Quin 2;    Ca2+ mobilization;    Platelet activation;    [Ca2+]i;    cytosolic free Ca2+ concentration;    Cao 2+;    external Ca2+;    Nao +;    external Na+;    IP3;    inositol 1;    4;    5-trisphosphate;    PIP2;    phosphatidylinositol 4;    5-bisphosphate;    PIP;    phosphatidylinositol 4-phosphate;    PI;    phosphatidylinositol;    PA;    phosphatidic acid;    EIPA;    ethylisopropylamiloride;   

DOI  :  10.1016/0014-5793(87)81569-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Stimulation of human platelets increases cytoplasmic pH (pH_i) via activation of Na⁺/H⁺ exchange. We have determined the effect of inhibiting Na⁺/H⁺ exchange on (i) thrombin-induced Ca²⁺ mobilization and (ii) turnover of ³²P-labelled phospholipids. Blocking Na⁺/H⁺ exchange by removal of extracellular Na⁺ or by ethylisopropylamiloride (EIPA) inhibited Ca²⁺ mobilization induced by 0.2 thrombin, whereas increasing pH_i by NH₄C1 enhanced the thrombin-induced increase in cytosolic free Ca²⁺. The effect of EIPA was bypassed after increasing pH_i by moneasin. The thrombin-induced cleavage of phosphatidylinositol 4,5-bisphosphate (PIP₂) was unaffected by treatments that blocked Na⁺/H⁺ exchange or increased pH_i. It is concluded that activation of Na⁺/H⁺ exchange is a prerequisite for Ca²⁺ mobilization in human platelets but not for the stimulus-induced hydrolysis of PIP₂.

【 授权许可】

Unknown