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