Dose-dependent inhibition of phosphoinositide metabolism in human platelets by aspirin in vitro and in vivo.
The effects of aspirin on the metabolism of phosphoinositides in human platelets were studied in vitro and in vivo. Eight volunteers received, at two-weekly intervals, a single dose of 10, 30, 100 or 600 mg aspirin. Before the first dose platelets were taken and incubated in vitro with a range of concentrations (10 nM-100 microM) of aspirin. Formation of inositol phosphates (IP) was measured in [3H]-inositol labelled platelets after incubation with collagen and thrombin for 30 min, a time at which a maximal increase in [3H]-IP was observed. The in vitro IC50 for inhibition of the response to collagen by aspirin was approximately 1 microM; the in vivo ID50 was 40-50 mg. Aspirin did not fully inhibit the collagen stimulated IP formation either in vitro or in vivo, and the response to thrombin was unaffected. The ID50 and IC50 of aspirin is thus in accord with the doses of aspirin associated with inhibition of platelet aggregation and thromboxane production in other studies. The possible relevance of these data to the clinical uses of aspirin is discussed.
D000328:Adult; D000368:Aged; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism*; D002986:Clinical Trials as Topic; D003094:Collagen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D010716:Phosphatidylinositols / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D011897:Random Allocation
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D003094:Collagen; D001241:Aspirin