Premium
Extracellular Na + removal enhances granule secretion in platelets 3‐evidence that Na + /H + exchange is inhibitory to secretion induced by some agonists
Author(s) -
Krishnamurthi Sushila,
Morgan Winston A.,
Kakkar Vijay V.
Publication year - 1989
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(89)80719-7
Subject(s) - secretion , extracellular , platelet , chemistry , granule (geology) , biophysics , biochemistry , medicine , biology , paleontology
The effect of extracellular Na + ([Na + ] e ) removal on agonist‐induced granule secretion in platelets in relation to [ph] i and [Ca 2+ ] 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 diC 8 . Increases in [Ca 2+ ] i induced by thrombin and U46619 were slightly inhibited or unaffected in these buffers, but [pH] i increases induced by thrombin, U46619, PMA and diC 8 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) NH 4 Cl, 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.