Kinetics of merthiolate-induced aggregation of human plateletsстатья

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[1] Kinetics of merthiolate-induced aggregation of human platelets / P. V. Vrzheshch, A. V. Tatarintsev, E. V. Orlova et al. // Thrombosis Research. — 1992. — Vol. 67, no. 5. — P. 505–516. 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. [ DOI ]

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