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 microns. In A23187-stimulated human polymorphonuclear leukocytes (PMNs), BMS-181162 blocked arachidonic acid release with an IC50 of 10 microns. 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 micrograms 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.
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Authors | 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 |
Journal | The Journal of pharmacology and experimental therapeutics
(J Pharmacol Exp Ther)
Vol. 271
Issue 2
Pg. 852-9
(Nov 1994)
ISSN: 0022-3565 [Print] United States |
PMID | 7965805
(Publication Type: Journal Article)
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Chemical References |
- Anti-Inflammatory Agents
- Eicosanoids
- Platelet Activating Factor
- 13-cis-12-(3'-carboxyphenyl)retinoic acid
- Arachidonic Acid
- Tretinoin
- Phospholipases A
- Phospholipases A2
- Tetradecanoylphorbol Acetate
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Topics |
- Administration, Topical
- Anti-Inflammatory Agents
(pharmacology)
- Arachidonic Acid
(metabolism)
- Dermatitis
(metabolism, prevention & control)
- Eicosanoids
(biosynthesis)
- Humans
- Neutrophils
(drug effects, metabolism)
- Phospholipases A
(antagonists & inhibitors)
- Phospholipases A2
- Platelet Activating Factor
(biosynthesis)
- Tetradecanoylphorbol Acetate
(pharmacology)
- Tretinoin
(analogs & derivatives, pharmacology)
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