Inhibition of arachidonic acid cyclo-oxygenase and lipoxygenase activities of leukocytes by indomethacin and compound BW755C.

Agents and actions ·Vol. 10 ·No. 6 ·1980-12-00 ·Pages 553-5

Randall RW, Eakins KE, Higgs GA, Salmon JA, Tateson JE

Abstract

Arachidonic acid is metabolized via two pathways in leukocytes: cyclo-oxygenase, leading to the stable prostaglandins, and lipoxygenase, leading to hydroxyacids. Indomethacin inhibits the cyclo-oxygenase selectively, whereas compound BW755C (3-amino-1-(m-(trifluoromethyl)phenyl)-2-pyrazoline) inhibits both pathways equally. This offers a possible explanation for the differing activities of these two compounds in inflammatory models in vivo. The patterns of product inhibition by the two compounds support the suggestion that 11-HETE (hydroxy-eicosate-traenoic acid) and 15-HETE can arise by incomplete operation of the cyclo-oxygenase pathway.

MeSH Terms

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine Animals Anti-Inflammatory Agents/pharmacology Arachidonic Acids/biosynthesis,metabolism Cyclooxygenase Inhibitors Indomethacin/pharmacology Leukocytes/enzymology Lipoxygenase Inhibitors Pyrazoles/pharmacology Rabbits

Chemicals

Anti-Inflammatory Agents Arachidonic Acids Cyclooxygenase Inhibitors Lipoxygenase Inhibitors Pyrazoles 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine Indomethacin

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Randall R W

Eakins K E

Higgs G A

Salmon J A

Tateson J E

References (5)

5 references, click to expand

Transformation of arachidonic acid and homo-gamma-linolenic acid by rabbit polymorphonuclear leukocytes. Monohydroxy acids from novel lipoxygenases.
J Biol Chem. 1976 Dec 25;251(24):7816-20 PMID: 826538
Leukotriene C: a slow-reacting substance from murine mastocytoma cells.
Proc Natl Acad Sci U S A. 1979 Sep;76(9):4275-9 PMID: 41240
Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs.
Nat New Biol. 1971 Jun 23;231(25):232-5 PMID: 5284360
Biogenesis of chemotactic molecules by the arachidonate lipoxygenase system of platelets.
Nature. 1975 Oct 23;257(5528):680-1 PMID: 810723
Aspirin-like drugs inhibit arachidonic acid metabolism via lipoxygenase and cyclo-oxygenase in rat neutrophils from carrageenan pleural exudates.
Biochem Biophys Res Commun. 1980 Jan 29;92(2):688-95 PMID: 6766725

Article Info

Journal

Agents and actions

Abbr.

Agents Actions

ISSN

0065-4299

DOI

10.1007/BF02024164

Published

1980-12-00

Pages

553-5

Language

English

Region

Switzerland

NLM ID

0213341

Subset

External Links

PubMed source DOI: 10.1007/BF02024164

Analysis Services

Inhibition of arachidonic acid cyclo-oxygenase and lipoxygenase activities of leukocytes by indomethacin and compound BW755C.

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