Diminished inhibition of adhesion molecule expression in prostacyclin receptor desensitized human platelets

Agents Actions Suppl. 1995:45:77-83. doi: 10.1007/978-3-0348-7346-8_12.

Abstract

Long-term exposure of platelets to prostacyclin or iloprost (100nM, 3hr) results in receptor desensitization measured as decrease in 3H-iloprost binding sites by 47 +/- 14%. Desensitized platelets respond with an increased adhesion to endothelial cells. The mechanism of increased adhesiveness was studied by measuring the expression of the adhesion molecule CD62p (p-selectin; GMP140) on washed human platelets by flowcytometry. In thrombin stimulated platelets CD62p expression was dose-dependently reduced by iloprost. In receptor desensitized platelets IC50 for iloprost inhibition of thrombin-induced CD62p expression increased from 0.48 +/- 0.10 to 2.4 +/- 0.7 nM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • Cell Adhesion Molecules / biosynthesis*
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Iloprost / metabolism*
  • Iloprost / pharmacology
  • P-Selectin
  • Platelet Membrane Glycoproteins / biosynthesis*
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / metabolism*
  • Receptors, Epoprostenol
  • Receptors, Prostaglandin / drug effects
  • Receptors, Prostaglandin / metabolism*
  • Thrombin / pharmacology

Substances

  • Cell Adhesion Molecules
  • P-Selectin
  • Platelet Membrane Glycoproteins
  • Receptors, Cell Surface
  • Receptors, Epoprostenol
  • Receptors, Prostaglandin
  • Thrombin
  • Iloprost