HIGH-DENSITY-LIPOPROTEINS ENHANCE THE NA+ H+ ANTIPORT IN HUMAN PLATELETS/

In the present study, we investigated the effect of high density lipop roteins 3 (HDL(3)) on Na+/H+ exchanger activity and cytosolic pH (pH(i )) in human platelets. HDL(3) alone failed to affect pH(i), but preinc ubation with HDL(3) significantly enhanced the Na+/H+ antiport activat ion brought about by acidification with 100 mM sodium propionate or st imulation with 0.05 U/ml thrombin. The stimulatory effect of HDL(3) wa s unaffected by indomethacin excluding a role for cyclooxygenase produ cts. The HDL(3) effect was not mediated by Ca2+/calmodulin-dependent p rotein kinase as HDL(3) failed to increase cytosolic free calcium conc entration. However, the potentiating effect of HDL(3) was completely b locked in the presence of the protein kinase C inhibitor, bisindoylmal eimide and the phosphatidylcholine-specific phospholipase C inhibitor, D609. Furthermore, the effect of HDL(3) was abolished after covalent modification of HDL(3) with dimethylsuberimidate and was not observed in platelets from Glanzmann thrombasthenia type 1 which do not express GP IIb/IIIa, as well as in platelets preincubated with anti-GP IIb/II Ia polyclonal antibodies. We conclude that HDL(3) enhances the sodium propionate- and thrombin-induced Na+/H+ antiport activity in human pla telets via binding to GP IIb/IIIa and activation of protein kinase C a nd phosphatidylcholine-specific phospholipase C.