Diminished inhibition of adhesion molecule expression in prostacyclin receptor desensitized human platelets.
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.
Darius
H
H
Department of Medicine II, Johannes Gutenberg-University, Mainz, Germany.
Veit
K
K
Binz
C
C
Fisch
A
A
Meyer
J
J
D000704:Analysis of Variance; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D016285:Iloprost / Q000378:metabolism* / Q000494:pharmacology; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D013917:Thrombin; D016285:Iloprost