Cell response kinetics: the phenomenon of supercooperativity in aggregation of human platelets

Thromb Res. 1992 Jun 1;66(5):537-47. doi: 10.1016/0049-3848(92)90308-w.

Abstract

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.

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Adenosine Diphosphate / pharmacology
  • Arachidonic Acid / pharmacology
  • Calcimycin / pharmacology
  • Epinephrine / pharmacology
  • Humans
  • Kinetics
  • Platelet Activating Factor / pharmacology
  • Platelet Aggregation / drug effects*
  • Prostaglandin Endoperoxides, Synthetic / pharmacology
  • Prostaglandin H2
  • Prostaglandins H / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thimerosal / pharmacology

Substances

  • Platelet Activating Factor
  • Prostaglandin Endoperoxides, Synthetic
  • Prostaglandins H
  • Thimerosal
  • Arachidonic Acid
  • Calcimycin
  • Prostaglandin H2
  • Adenosine Diphosphate
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Tetradecanoylphorbol Acetate
  • Epinephrine