Cell response kinetics: the phenomenon of supercooperativity in aggregation of human platelets.
Concentration-response relationships of human platelet aggregation rates were analyzed for a variety of agonists and inhibitors. Their approximation by the Hill equation showed that the values of the Hill coefficient (h) were agonist-dependent and increased as follows: hADP = hL-EPINEPHRINE = hPAF = hPGH2 = hU46619 less than hPMA less than hA23187 less than hMERTHIOLATE = hARACHIDONATE. The results were interpreted in terms of a model assuming varying degrees of cooperativity for each step of signal transduction involved in platelet aggregation. Super-high values of h (greater than 30) obtained with arachidonate and merthiolate, as well as in the case of inhibition of an arachidonate-induced response by indomethacin and PTA2, suggested that at least one region of signal transduction pathway leading to aggregation exhibited supercooperative properties.
Vrzheshch
P V
PV
A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Russia.
Tatarintsev
A V
AV
Yershov
D E
DE
Varfolomeyev
S D
SD
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D010972:Platelet Activating Factor / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013849:Thimerosal / Q000494:pharmacology
D010972:Platelet Activating Factor; D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D013849:Thimerosal; D016718:Arachidonic Acid; D000001:Calcimycin; D044262:Prostaglandin H2; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D013755:Tetradecanoylphorbol Acetate; D004837:Epinephrine