Inhibition of alveolar macrophage 5-lipoxygenase metabolism by auranofin

Biochemical Pharmacology
M Peters-Golden, C Shelly

Abstract

We have examined the effect of the oral gold compound auranofin (AF) on calcium ionophore A23187-induced arachidonic acid metabolism in the rat alveolar macrophage. Both reverse-phase high performance liquid chromatographic and radioimmunoassay analyses revealed that AF dose-dependently inhibited leukotriene B4 and 5-hydroxyeicosatetraenoic acid synthesis in a parallel fashion with an IC50 approximately 4.3 micrograms/ml. At the same time, AF augmented A23187-induced arachidonate release and cyclooxygenase metabolism. A possible mechanism for the inhibition of 5-lipoxygenase was suggested by the capacity of AF to dose-dependently deplete ATP (IC50 approximately 5.9 micrograms/ml), a cofactor for 5-lipoxygenase. These data indicate that, at therapeutic concentrations, AF acts in vitro as a selective inhibitor of macrophage 5-lipoxygenase metabolism. This likely represents an important mechanism of action of AF in chronic inflammatory disorders.

References

Dec 1, 1985·Journal of Applied Physiology·P M O'ByrneJ A Nadel
Jan 1, 1988·The American Review of Respiratory Disease·P H SpornR H Simon
Nov 1, 1988·The American Review of Respiratory Disease·M S BalterM Peters-Golden
Jan 1, 1988·The Journal of Allergy and Clinical Immunology·D I BernsteinR G Pietrusko
Aug 1, 1987·Seminars in Arthritis and Rheumatism·R M SnyderS T Crooke
Oct 1, 1987·The American Review of Respiratory Disease·P M O'ByrneJ G Kirby
Sep 1, 1985·Biochemical Pharmacology·I Ahnfelt-Rønne, U B Olsen
Dec 1, 1984·The Journal of Allergy and Clinical Immunology·N YamauchiT Miyamoto
Jul 4, 1981·Lancet·M C HolroydeE V Elliott
Oct 31, 1983·The American Journal of Medicine·P E Lipsky
Apr 1, 1982·The Journal of Experimental Medicine·W A ScottZ A Cohn
May 1, 1980·The Journal of Investigative Dermatology·P DaviesF A Kuehl

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Citations

May 1, 1997·European Journal of Pharmacology·M YamashitaK Ohuchi
Feb 14, 2006·American Journal of Respiratory Cell and Molecular Biology·Megan N BallingerBethany B Moore
Nov 1, 1995·The British Journal of Psychiatry : the Journal of Mental Science·D Taylor

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