High density lipoproteins enhance the Na+/H+ antiport in human platelets.
In the present study, we investigated the effect of high density lipoproteins 3 (HDL3) on Na+/H+ exchanger activity and cytosolic pH (pHi) in human platelets. HDL3 alone failed to affect pHi, but preincubation with HDL3 significantly enhanced the Na+/H+ antiport activation brought about by acidification with 100 mM sodium propionate or stimulation with 0.05 U/ml thrombin. the stimulatory effect of HDL3 was unaffected by indomethacin excluding a role for cyclooxygenase products. The HDL3 effect was not mediated by Ca2+/calmodulin-dependent protein kinase as HDL3 failed to increase cytosolic free calcium concentration. However, the potentiating effect of HDL3 was completely blocked in the presence of the protein kinase C inhibitor, bisindoylmaleimide and the phosphatidylcholine-specific phospholipase C inhibitor, D609. Furthermore, the effect of HDL3 was abolished after covalent modification of HDL3 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/IIIa polyclonal antibodies. We conclude that HDL3 enhances the sodium propionate- and thrombin-induced Na+/H+ antiport activity in human platelets via binding to GP IIb/IIIa and activation of protein kinase C and phosphatidylcholine-specific phospholipase C.
Nofer
J R
JR
Institut für Klinische Chemie und Laboratoriumsmedizin, Zentrallaboratorium, Münster, Germany.
Tepel
M
M
Kehrel
B
B
Walter
M
M
Seedorf
U
U
Assmann
G
G
Zidek
W
W
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000097:blood; D004789:Enzyme Activation; D006801:Humans; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000097:blood; D010740:Phospholipases / Q000378:metabolism; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D012965:Sodium Chloride / Q000097:blood; D017923:Sodium-Hydrogen Exchangers / Q000097:blood / Q000187:drug effects*; D013379:Substrate Specificity; D013917:Thrombin / Q000494:pharmacology
D008075:Lipoproteins, HDL; D010713:Phosphatidylcholines; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011422:Propionates; D017923:Sodium-Hydrogen Exchangers; D012965:Sodium Chloride; C514135:sodium propionate; D011493:Protein Kinase C; D010740:Phospholipases; D013917:Thrombin; C029658:propionic acid; D002118:Calcium