Study of inhibitors of the PGH synthases for which potency is regulated by the redox state of the enzymes.
Aspirin, salicylic acid, and acetaminophen are examples of drugs that inhibit the PGH synthases (cyclooxygenases) with potencies that vary remarkably between different cells. This results from the fact that the inhibitory action of these drugs is regulated by redox cycling of the enzymes, which is determined by the concentration of hydroperoxides in the enzyme proximity. The potency of these drugs is greatest in the presence of low concentrations of hydroperoxides. Accordingly, analysis of the action of these inhibitors requires consideration of assay conditions that take into account the factors that control hydroperoxide concentrations, both in studies with purified enzymes and in cells.
Boutaud
Olivier
O
Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
Oates
John A
JA
D000082:Acetaminophen / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D045744:Cell Line, Tumor; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D010084:Oxidation-Reduction; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D020156:Salicylic Acid / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D016718:Arachidonic Acid; D000082:Acetaminophen; D013929:Thromboxane B2; D006861:Hydrogen Peroxide; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D020156:Salicylic Acid; D001241:Aspirin