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Supercooperativity in platelet aggregation: Substituted pyridyl isoxazoles, a new class of supercooperative platelet aggregation inhibitors
Author(s) -
Vrzheshch Peter V.,
Demina Olga V.,
Shram Stanislav I.,
Varfolomeev Sergey D.
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)00845-0
Subject(s) - platelet , chemistry , platelet aggregation , cyclooxygenase , thromboxane a2 , inducer , thromboxane , thromboxane b2 , thromboxane a synthase , biochemistry , enzyme , stereochemistry , biophysics , arachidonic acid , medicine , biology , receptor , gene
The phenomenon of supercooperativity in platelet aggregation is manifested by the occurence of clear‐cut thresholds in dose—response relationships; in such cases the Hill coefficient has unusually high values. Approximation, by the Hill equation, of the relationship of the rate of arachidonate‐induced platelet aggregation to the concentrations of either the inducer or inhibitors such as substituted pyridyl isoxazoles (synthesized by us), indomethacin, and pinane thromboxane A 2 , demonstrated that the Hill coefficients ranged from 30 to 100. 3‐(3‐Pyridyl)‐5‐phenylisoxazole, which exhibited maximal anti‐aggregatory activity among the synthesized compounds, inhibited neither cyclooxygenase nor thromboxane synthase. The compounds affected the signal transduction pathway at/or posterior to the stage of thromboxane A 2 reception.