A phorbol ester and 1-oleoyl-2-acetylglycerol induce Na+/H+ exchange in human platelets.
This study aimed at investigating the mechanisms by which stimulation of human platelets results in activation of Na+/H+ exchange. Platelets were suspended in a slightly buffered medium and the stimulus-induced, amiloride-sensitive H+ release, reflecting Na+/H+ exchange, was estimated from changes in the medium pH. H+ release could be evoked by thrombin and by activators of protein kinase C such as 1-oleoyl-2-acetylglycerol (OAG) or 12-O-tetradecanoylphorbol-13-acetate (TPA). Both the thrombin-and the OAG-induced Na+/H+ exchange could be blocked by trifluoperazine, a protein kinase C inhibitor. The thrombin-induced H+ release was also sensitive to increased intracellular cAMP levels, probably due to inhibition of phospholipase C activation, whereas the OAG-induced activation of Na+/H+ exchange was unaffected. Our data suggest that activation of Na+/H+ exchange is mediated by protein kinase C.
D000527:Alprostadil / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002352:Carrier Proteins / Q000097:blood*; D004075:Diglycerides / Q000494:pharmacology*; D011464:Epoprostenol / Q000494:pharmacology; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D011493:Protein Kinase C / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism; D014268:Trifluoperazine / Q000494:pharmacology
D002352:Carrier Proteins; D004075:Diglycerides; D005989:Glycerides; D017923:Sodium-Hydrogen Exchangers; D014268:Trifluoperazine; D000001:Calcimycin; D003994:Bucladesine; C038237:1-oleoyl-2-acetylglycerol; D011464:Epoprostenol; D011493:Protein Kinase C; D013917:Thrombin; D000527:Alprostadil; D013755:Tetradecanoylphorbol Acetate