Kinetics of merthiolate-induced aggregation of human platelets.
Incubation of human platelet-rich plasma (PRP) or washed platelets with merthiolate (MT; sodium ethylmercurithiosalicylate; an inhibitor of lysophosphatide: arachidonoyl transferase) leads to irreversible platelet aggregation which is parallelled by an increase in thromboxane A2 synthesis. MT-induced aggregation is preceded by a pronounced lag-period (0.5-10 min). Duration of the latter is inversely related to the concentration of MT ([MT]). Platelet responses to MT are similar to those triggered by arachidonate (AA) in that the relationships of the aggregation rates both to [MT] and [AA] are threshold and exhibit characteristic super-high values of the apparent Hill coefficients (h > 30). A typical MT-induced response can be subdivided in two sequential phases: i) cyclooxygenase-independent slow aggregation, and ii) indomethacin-abrogated rapid aggregation. MT-induced responses are blocked by PGE1 or ajoene (which inhibits binding of fibrinogen to its cell surface receptor, GPIIb/IIIa). The obtained data are interpreted both quantitatively and qualitatively in terms of a model assuming the existence of: i) a relationship between the rate of MT-inhibitable AA incorporation into phospholipids and the concentration of intracellular free AA, [AA]i; ii) a certain threshold value of [AA]i essential for triggering the second phase of the aggregation.
Vrzheshch
P V
PV
Bio-Rad Laboratories T.O. BioChemMack, Moscow, Russia.
Tatarintsev
A V
AV
Orlova
E V
EV
Yershov
D E
DE
Varfolomeyev
S D
SD
D000527:Alprostadil / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D004220:Disulfides / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008954:Models, Biological; D010936:Plant Extracts / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D013454:Sulfoxides; D013849:Thimerosal / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis
D004220:Disulfides; D010936:Plant Extracts; D010980:Platelet Membrane Glycoproteins; D013454:Sulfoxides; D013849:Thimerosal; D016718:Arachidonic Acid; D013928:Thromboxane A2; C048980:ajoene; D000527:Alprostadil; D007213:Indomethacin