Adhesion of human platelets to collagen in the presence of prostacyclin, indomethacin and compound BW 755C.
Prostacyclin (1 ng to 2 micrograms per ml), which effectively inhibits platelet secretion and aggregation, does not affect adhesion of a proportion of platelets (10-38%) to collagen (50-100 micrograms/ml). Adhesion is not detectable by changes of light transmission (as measured in the optical aggregometer) and is not affected by inhibitors of cyclooxygenase and lipoxygenase enzymes such as indomethacin and compound BW 755C. This adhesion is independent of the collagen concentration (50-400 micrograms/ml) and the incubation time (5-20 min). This suggests that adhesion to collagen is related to a specific platelet population. Adhesion in the presence of prostacyclin, indomethacin and BW 755C occurs in parallel with the formation of a limited amount of phosphatidic acid. Under those conditions it is also possible to observe some phosphorylation of a 40,000 dalton protein which is a substrate for protein kinase C activity. Phosphorylation of the 20,000 dalton protein, or myosin light chain, is less evident. Chlorpromazine (25-100 micrograms/ml) inhibited the adhesion of platelets to collagen, but propanolol (0.5-4 microM) was inactive. The adhesion of platelets to collagen in these experiments parallels the formation of a fraction of phosphatidic acid and 40,000 dalton protein phosphorylation, which are independent of the increased levels of platelet cyclic-AMP induced by high concentrations of prostacyclin. It is also independent of the formation of cyclooxygenase or lipoxygenase products.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000328:Adult; D001798:Blood Proteins / Q000378:metabolism; D002746:Chlorpromazine / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism; D011464:Epoprostenol / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D010712:Phosphatidic Acids / Q000097:blood; D010766:Phosphorylation; D010973:Platelet Adhesiveness / Q000187:drug effects*; D011493:Protein Kinase C / Q000097:blood; D011720:Pyrazoles / Q000494:pharmacology*
D001798:Blood Proteins; D010712:Phosphatidic Acids; D011720:Pyrazoles; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D003094:Collagen; D011464:Epoprostenol; D011493:Protein Kinase C; D002746:Chlorpromazine; D007213:Indomethacin