PMID: 2505061May 4, 1989Paper

Differential effects of ibuprofen, indomethacin, and meclofenamate on prostaglandin endoperoxide H2 metabolism

Molecular and Cellular Biochemistry
P R MayeuxD B McNamara

Abstract

Previous studies have suggested the possibility that the non-steroidal antiflammatory drug (NSAID), ibuprofen, may inhibit thromboxane (TX) A2 synthase activity in addition to inhibiting cyclooxygenase activity. Microsomal fractions isolated from the cat lung contain cyclooxygenase as well as prostacyclin (PGI2) synthase, TX synthase, and a GSH-dependent prostaglandin (PG) E2 isomerase activities. When [1-14C] PG endoperoxide H2 (PGH2) was used as substrate, ibuprofen, indomethacin, and meclofenamate exhibited differential effects on terminal enzyme activities. Ibuprofen, at concentrations up to 1 mM, had no effect on the activities of PGI2 synthase, TXA2 synthase of GSH-dependent PGE2 isomerase, whereas indomethacin selectively inhibited PGI2 synthase activity at 5 X 10(-4) M and 10(-3) M. Meclofenamate selectively inhibited TXA2 synthase activity at 5 X 10(-4) M and 10(-3) M. At concentrations of 5 X 10(-3) M, this selectivity was not observed, and indomethacin and meclofenamate decreased the formation of both 6-keto-PGF1 alpha and TXB2. These data indicate that the choice of NSAID and the concentration employed may specifically alter PGH2 metabolism. This action may affect the physiologic consequences of the exchange of PGH2...Continue Reading

References

Jan 1, 1979·Thrombosis Research·G Rajtar, G de Gaetano
Sep 1, 1986·Journal of Applied Physiology·M R LittnerF D Lott
Jan 1, 1988·Arteriosclerosis : an Official Journal of the American Heart Association, Inc·D S RushD B McNamara
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Jan 13, 1984·Biochemical and Biophysical Research Communications·D B McNamaraP J Kadowitz
Mar 1, 1984·Prostaglandins, Leukotrienes, and Medicine·M E SoulsbyR C Bone
Nov 1, 1980·The Journal of Clinical Investigation·A J MarcusM J Broekman
Apr 1, 1981·Prostaglandins·H S SheP J Kadowitz
Sep 1, 1982·The Journal of Clinical Investigation·E R JacobsF C Hiller

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Citations

Sep 5, 2002·Clinical and Experimental Pharmacology & Physiology·Jeremy J OliverRoger G Evans
Jan 1, 1992·European Journal of Clinical Pharmacology·M CagossiG Salgarello

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