PMID: 6410393Jul 1, 1983Paper

Inhibition of a major NAD(P)-linked oxidoreductase from rat liver cytosol by steroidal and nonsteroidal anti-inflammatory agents and by prostaglandins

Proceedings of the National Academy of Sciences of the United States of America
T M Penning, P Talalay

Abstract

A NAD(P)-linked 3 alpha-hydroxysteroid dehydrogenase [3 alpha-hydroxysteroid: NAD(P) oxidoreductase, EC 1.1.1.50], purified to homogeneity from male rat liver cytosol, accounts for most of the oxidative activity for 3 alpha-hydroxysteroids and for benzenedihydrodiol (trans-1,2-dihydroxy-3,5-cyclohexadiene) of this tissue. This enzyme, which also promotes the reduction of quinones and certain aromatic aldehydes and ketones, is powerfully inhibited by the major types of nonsteroidal and steroidal anti-inflammatory drugs. The IC50 values for indomethacin and for betamethasone are in the low micromolar range. The rank order of the inhibitory potencies of a series of these agents paralleled closely that reported for the inhibition of cyclooxygenase by nonsteroidal anti-inflammatory agents or the indirect inhibition of phospholipase A2 by anti-inflammatory steroids. A good correlation is found also between the logarithm of the concentrations of these drugs required to inhibit 3 alpha-hydroxysteroid dehydrogenase and the human anti-inflammatory dose. The suggestion that this enzyme may play a role in mediating inflammation is further strengthened by the observation that the dehydrogenase binds arachidonic acid and is also potentially ...Continue Reading

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Citations

Jan 1, 1994·Cytotechnology·S I GrammatikosW M Miller
Mar 15, 1985·Biochemical Pharmacology·T E Smithgall, T M Penning
Dec 1, 1986·Biochemical Pharmacology·T M Penning
Oct 1, 1985·Journal of Steroid Biochemistry·D A SirettG G Rousseau
Oct 1, 1988·Journal of Steroid Biochemistry·G G RousseauJ I Quivy
Apr 1, 1986·Steroids·T M PenningR B Sharp
Nov 1, 1991·Steroids·W M Mok, N R Krieger
Oct 1, 1992·The Journal of Steroid Biochemistry and Molecular Biology·R B IyerA L Southren
Dec 1, 1993·The Journal of Steroid Biochemistry and Molecular Biology·K N QinK C Cheng
Sep 1, 1996·Steroids·T M PenningM Lewis
Jun 4, 1998·Pharmacology, Biochemistry, and Behavior·O González-FloresC Beyer
Mar 29, 1994·Proceedings of the National Academy of Sciences of the United States of America·S S HoogM Lewis
Sep 15, 2006·Annual Review of Pharmacology and Toxicology·Yi Jin, Trevor M Penning
Mar 1, 1997·Drug Metabolism and Drug Interactions·S Fayz, T Inaba
Oct 25, 2008·Drug Metabolism Reviews·Oleg A BarskiAruni Bhatnagar
Jan 29, 2011·The Journal of Steroid Biochemistry and Molecular Biology·Trevor M Penning
Nov 20, 2010·The Journal of Steroid Biochemistry and Molecular Biology·Michael C ByrnsTrevor M Penning
Mar 3, 2009·Annals of the New York Academy of Sciences·Trevor M Penning, Michael C Byrns
Oct 29, 1987·Biochemical and Biophysical Research Communications·T M Penning, R B Sharp
Feb 22, 2012·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Jillissa C Molnari, Alan L Myers
Jun 12, 2013·The Journal of Steroid Biochemistry and Molecular Biology·Adegoke O AdenijiTrevor M Penning
May 1, 1994·Journal of Pharmaceutical Sciences·V Garg, W J Jusko

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