Inhibitor of phospholipase A2 blocks eicosanoid and platelet activating factor biosynthesis and has topical anti-inflammatory activity

K. M. Tramposch, F. H. Chilton, P. L. Stanley, R. C. Franson, M. B. Havens, D. O. Nettleton, L. B. Davern, I. M. Darling, R. J. Bonney

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The effect of a phospholipase A2 (PLA2) inhibitor on leukotriene, prostaglandin and platelet activating factor (PAF) biosynthesis in isolated cells and in vivo was determined. BMS-181162, [4(3'-carboxyphenyl)-3,7- dimethyl-9(2'',6'',6''-trimethyl-1''-cyclohexenyl),2Z,4E,6E,8E-nonatetraenoic acid], reversibly inhibited the 14-kdalton PLA2 purified from human synovial fluid with an IC50 of 8 μm. In A23187-stimulated human polymorphonuclear leukocytes (PMNs), BMS-181162 blocked arachidonic acid release with an IC50 of 10 μm. Leukotriene B4 and PAF biosynthesis in these cells was also inhibited. In a phorbol ester-induced chronic mouse skin inflammation model, topically applied BMS-181162 markedly lowered the tissue levels of leukotriene B4 and prostaglandin E2 and dose-dependently inhibited leukocyte infiltration (ED50 = 180 μg per ear). BMS-181162 is an inhibitor of PLA2 and may prove to be a useful tool in the delineation of the role of PLA2 in the inflammatory process.

Original languageEnglish (US)
Pages (from-to)852-859
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume271
Issue number2
StatePublished - 1994
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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