Superoxide dismutase cooperates with prostacyclin to inhibit platelet aggregation: a comparative study in washed platelets and platelet rich plasma.
The role of superoxide anions (O2-) in human platelet aggregation in Krebs' buffer or plasma was investigated. In indomethacin (10 microM)-treated washed platelets superoxide dismutase (SOD; 60 U/ml) or ferricytochrome c (FCC; 70 microM) inhibited platelet aggregation by thrombin but not that by collagen or ADP. In addition, in indomethacin (10 microM)-treated washed platelets, SOD significantly potentiated the anti-aggregatory activity of prostacyclin (PGI2) or iloprost when thrombin but not collagen was used as the aggregating agent. In platelet rich plasma, SOD (60 U/ml) did not inhibit platelet aggregation nor did it potentiate the anti-aggregatory activity of iloprost when ADP, collagen or thrombin were used as aggregating agents. Thus, O2- participate in the aggregatory activity of thrombin but not collagen or ADP and PGI2 or iloprost, by reducing the sensitivity of platelets to thrombin, co-operate with SOD to inhibit thrombin-induced platelet aggregation. The interpretation of the use of SOD in experiments involving endothelium-derived relaxing factor (NO) is discussed.
Salvemini
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William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, United Kingdom.
de Nucci
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G
Vane
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JR
D000244:Adenosine Diphosphate / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D004347:Drug Interactions; D011464:Epoprostenol / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013481:Superoxides / Q000097:blood; D013917:Thrombin / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D013481:Superoxides; D000244:Adenosine Diphosphate; D003094:Collagen; D011464:Epoprostenol; D013482:Superoxide Dismutase; D013917:Thrombin; D007213:Indomethacin