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Inhibition of Na + /H + exchange reduces Ca 2+ mobilization without affecting the initial cleavage of phosphatidylinositol 4,5‐bisphosphate in thrombin‐stimulated platelets
Author(s) -
Siffert W.,
Siffert G.,
Scheid P.,
Riemens T.,
Gorter G.,
Akkerman J.W.N.
Publication year - 1987
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(87)81569-7
Subject(s) - chemistry , phosphatidylinositol , cleavage (geology) , radiochemistry , biochemistry , biology , signal transduction , paleontology , fracture (geology)
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 Ca 2+ mobilization and (ii) turnover of 32 P‐labelled phospholipids. Blocking Na + /H + exchange by removal of extracellular Na + or by ethylisopropylamiloride (EIPA) inhibited Ca 2+ mobilization induced by 0.2thrombin, whereas increasing pH i by NH 4 C1 enhanced the thrombin‐induced increase in cytosolic free Ca 2+ . The effect of EIPA was bypassed after increasing pH i by moneasin. The thrombin‐induced cleavage of phosphatidylinositol 4,5‐bisphosphate (PIP 2 ) 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 Ca 2+ mobilization in human platelets but not for the stimulus‐induced hydrolysis of PIP 2 .