1650650

pubmed:Citation

5

The effects of U46619, a thromboxane mimic, on cytosolic Ca2+ concentration and platelet aggregation were determined in human platelets. Cytosolic Ca2+ concentration was determined by Quin-2 fluorescence and platelet aggregation quantitated with an aggregometer. Addition of U46619 (1 x 10(-7) M) to the platelet suspension produced a rapid increase in cytosolic Ca2+ and platelet aggregation. Pretreatment of platelets with EGTA (3 x 10(-3) M), verapamil (5 x 10(-4) M), a calcium entry blocker, or 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (1 x 10(-3) M), an inhibitor of intracellular Ca2+ release, either blunted or markedly delayed the rate, but not the magnitude, of increase in cytosolic Ca2+ and prevented platelet aggregation by U46619. Pretreatment of platelets with prostaglandin I2 (PGI2) (5 x 10(-8) M), PGD2 (5 x 10(-8) M), PGE1 (5 x 10(-8) M), PGF2 alpha (1 x 10(-5) M), dibutyryl cAMP (5 x 10(-3) M), or forskolin (1 x 10(-6) M) prevented both the increase in cytosolic Ca2+ and the associated platelet aggregation induced by U46619. These data suggest that U46619 may induce platelet aggregation through an increase in cytosolic Ca2+, and that both Ca2+ entry and its release from intracellular storage sites probably contribute to the increase in cytosolic Ca2+. Furthermore, the rate of the increase in cytosolic Ca2+ concentration, as well as the magnitude of the increase, appear to be critical for platelet aggregation induced by U46619. Our data are consistent with the hypothesis that PGs inhibit U46619-induced platelet aggregation by preventing the increase in cytosolic Ca2+, and that these effects may be mediated via an increase in cAMP, since they were induced by PGs and cAMP.

eng

IM

MEDLINE

0008-4212

Print

NLM

599-604

pubmed-meshheading:1650650-15-Hydroxy-11 alpha,9..., pubmed-meshheading:1650650-Adult, pubmed-meshheading:1650650-Bucladesine, pubmed-meshheading:1650650-Calcium, pubmed-meshheading:1650650-Calcium Channel Blockers, pubmed-meshheading:1650650-Cyclic AMP, pubmed-meshheading:1650650-Cytosol, pubmed-meshheading:1650650-Egtazic Acid, pubmed-meshheading:1650650-Female, pubmed-meshheading:1650650-Forskolin, pubmed-meshheading:1650650-Gallic Acid, pubmed-meshheading:1650650-Humans, pubmed-meshheading:1650650-Male, pubmed-meshheading:1650650-Platelet Aggregation, pubmed-meshheading:1650650-Platelet Aggregation Inhibitors, pubmed-meshheading:1650650-Prostaglandin Endoperoxides, Synthetic, pubmed-meshheading:1650650-Prostaglandins, pubmed-meshheading:1650650-Thromboxane A2, pubmed-meshheading:1650650-Verapamil

Effects of prostaglandins, cAMP, and changes in cytosolic calcium on platelet aggregation induced by a thromboxane A2 mimic (U46619).

Journal Article, Research Support, U.S. Gov't, P.H.S.