Extracellular Na+ removal enhances granule secretion in platelets 3‐evidence that Na+/H+ exchange is inhibitory to secretion induced by some agonists

FEBS Letters

Krishnamurthi, Sushila¹  Morgan, Winston A.¹  Kakkar, Vijay V.¹ 

[1] Thrombosis Research Unit, King's College School of Medicine and Dentistry, Rayne Institute, 123 Coldharbour Lane, London SE5 9NU, England

关键词: Na+/H+ exchange;    Platelet;    Secretion;    [pH]i;    intracellular pH;    [Ca2+]i;    intracellular Ca2+;    PMA;    phorbol 12-myristate 13-acetate;    diC8;    1;    2-dioctanoylglycerol;    [Na+]e;    extracellular Na+;   

DOI  :  10.1016/0014-5793(89)80719-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The effect of extracellular Na⁺ ([Na⁺]_e) removal on agonist-induced granule secretion in platelets in relation to [ph]_i and [Ca²⁺]_i changes was investigated. Substitution of [Na⁺]_e with choline⁺ of K⁺ resulted in a significant enhancement of 5HT secretion induced by thrombin, collagen, U46619 and the protein kinase C activators, PMA and diC₈. Increases in [Ca²⁺]_i induced by thrombin and U46619 were slightly inhibited or unaffected in these buffers, but [pH]_i increases induced by thrombin, U46619, PMA and diC₈ were abolished and a drop in [pH]_i (0.05–0.1 units below resting) was observed. Although preincubation with potassium acetate produced a big drop in [pH]_i and greatly increased secretion with all the agonists, particularly in the absence of [Na⁺]_e, clear evidence that [pH]_i rises due to Na⁺/H⁺ exchange are inhibitory to secretion was obtained only with thrombin. Thus, (i) NH₄Cl, which restored the increase in [pH]_i in the absence of [Na⁺]_e reduced the potentiated secretory response to thrombin, (ii) no increase in thrombin-induced secretion was observed when Na⁺ was replaced with Li⁺, which allowed a normal increase in [pH]_i and (iii) ethyl isopropyl amiloride (EIPA) abolished the [pH]_i rise and potentiated thrombin-induced secretion. With collagen and U46619, the results suggest that removal of [Na⁺]_e per se rather than inhibition of Na⁺/H⁺ exchange results in enhanced secretion. It is concluded that [Na⁺]_e per se and [pH]_i elevations via Na⁺/H⁺ exchange both have important inhibitory roles in the control of platelet granule secretion.

【 授权许可】

Unknown