Glutathione disulfide production during arachidonic acid oxygenation in human platelets.
Washed human platelets stimulated with 50 microM sodium arachidonate rapidly accumulated glutathione disulfide to a peak concentration of 0.620 nmole per 10(9) cells, 200% of control (unstimulated) levels. Total glutathione remained unchanged. The rise in glutathione disulfide was transitory, returning to control values within 30 seconds in aggregating platelets. Similar findings were observed in washed platelets aggregated with 5 U/ml thrombin. Platelet aggregation was not necessary for the generation of glutathione disulfide. However, cyclooxygenase activity was necessary for the generation of glutathione disulfide. Aspirin treated platelets aggregated with thrombin demonstrated no thromboxane B2 production and no glutathione disulfide generation. Dose response studies with both agonists demonstrated a direct relationship between the amount of thromboxane B2 produced and the amount of glutathione disulfide generated by stimulated platelets. During the conversion of arachidonic acid to thromboxane B2, unesterified arachidonic acid is oxygenated to prostaglandin G2 which is subsequently reduced to prostaglandin H2. Both reactions are catalyzed by the enzyme prostaglandin H synthase. Our data support the hypothesis that glutathione is an important supplier of reducing equivalents to prostaglandin H synthase during the production of prostaglandin H2 in human platelets.
Burch
J W
JW
American Red Cross Blood Services, Rochester, New York 14607.
Burch
P T
PT
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood* / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000097:blood; D019803:Glutathione Disulfide; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000097:blood; D044262:Prostaglandin H2; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D011463:Prostaglandins H / Q000097:blood; D013917:Thrombin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood
D001095:Arachidonic Acids; D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D016718:Arachidonic Acid; D044262:Prostaglandin H2; D013929:Thromboxane B2; D011451:Prostaglandin-Endoperoxide Synthases; D013917:Thrombin; D005978:Glutathione; D001241:Aspirin; D019803:Glutathione Disulfide