Activation of human platelets by N-substituted aminophospholipids.
N-(7-nitro-2,1,3-benzoxadiazol-4-yl) phosphatidylserine (NBD-PS), a fluorescent phospholipid synthesized from phosphatidylserine by reaction with NBD-chloride, caused platelet shape change and aggregation when added at micromolar concentrations to suspensions of washed human platelets in the absence of added fibrinogen. Platelet aggregation by NBD-PS was accompanied by thromboxane synthesis and secretion of contents from dense, alpha-, and lysosomal granules in the absence of appreciable platelet damage. Indomethacin completely inhibited NBD-PS-induced thromboxane synthesis, but platelet aggregation and [14C]serotonin secretion were only slightly inhibited. Neither inhibition of the ADP-dependent pathway with creatine phosphate/creatine kinase plus ATP, alone or in combination with indomethacin, nor maximum elevation of cyclic AMP by treatment with prostaglandin I2 and theophylline completely inhibited NBD-PS-induced platelet aggregation or [14C]serotonin secretion. Platelet effects of NBD-PS were specific in that neither phosphatidylserine nor lyso-NBD-PS were similarly active. The activation of platelets by NBD-PS is not attributable to the NBD moiety exclusively since acylation of the amino group with 5-dimethylaminonaphthalene-1-sulfonyl-chloride yielded a similarly active derivative. Dansylated phosphatidylethanolamine was also active. The findings indicate that NBD-PS and other N-substituted aminophospholipids can activate a central pathway of platelet secretion and aggregation that is independent of released ADP and thromboxane formation and is only partially controlled by platelet cyclic AMP.
Martin
T W
TW
Joist
J H
JH
Bauman
J E
JE
Lagunoff
D
D
D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives*; D000244:Adenosine Diphosphate / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects*; D000242:Cyclic AMP / Q000097:blood; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D010718:Phosphatidylserines / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology; D013928:Thromboxane A2 / Q000096:biosynthesis
C034296:N-(7-nitro-2,1,3-benzoxadiazol-4-yl)phosphatidylserine; D010718:Phosphatidylserines; D012701:Serotonin; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D013806:Theophylline; D011464:Epoprostenol; D000242:Cyclic AMP; D009327:4-Chloro-7-nitrobenzofurazan; D007213:Indomethacin