Document Detail


Essential fatty acids are antagonists of the leukotriene B4 receptor.
MedLine Citation:
PMID:  7630916     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A series of essential fatty acids and fatty acid derivatives were evaluated for their ability to inhibit [3H] leukotriene B4 (LTB4) binding to pig neutrophil membranes. The fatty acids varied in chain length, extent of unsaturation, position of unsaturation, and isomerization. Generally, fatty acids with two or more unsaturated sites and chain lengths of 18-22 were potent inhibitors of [3H]LTB4 binding; both n-3 and n-6 fatty acids were inhibitory. The most potent compounds tested were homogammalinolenic acid and ricinelaidic acid which gave Ki values of 1 microM and 2 microM in the binding assay. Ricinelaidic acid was also tested for its ability to inhibit LTB4-mediated chemotaxis (IC50 = 10 microM) and LTB4-induced calcium fluxes (IC50 = 7 microM) in isolated human neutrophils. Ricinelaidic acid did not show agonist activity in these assays. In an in vivo model of LTB4-induced bronchoconstriction, ricinelaidic acid and homogammalinolenic acid gave 46% and 53% inhibition, respectively, at a 1 mg/kg i.v. dose. These results indicate that essential fatty acids are LTB4 receptor antagonists, which may account in part for their reported anti-inflammatory activities.
Authors:
K A Yagaloff; L Franco; B Simko; B Burghardt
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Prostaglandins, leukotrienes, and essential fatty acids     Volume:  52     ISSN:  0952-3278     ISO Abbreviation:  Prostaglandins Leukot. Essent. Fatty Acids     Publication Date:  1995 May 
Date Detail:
Created Date:  1995-09-05     Completed Date:  1995-09-05     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  8802730     Medline TA:  Prostaglandins Leukot Essent Fatty Acids     Country:  SCOTLAND    
Other Details:
Languages:  eng     Pagination:  293-7     Citation Subset:  IM    
Affiliation:
Department of Metabolic Disease Research, Hoffmann-La Roche, Nutley, NJ 07110, USA.
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MeSH Terms
Descriptor/Qualifier:
8,11,14-Eicosatrienoic Acid / pharmacology
Animals
Bronchoconstriction / drug effects
Calcium / metabolism
Cell Membrane / metabolism
Chemotaxis, Leukocyte / drug effects
Fatty Acids, Essential / pharmacology*
Fatty Acids, Unsaturated / pharmacology
Humans
Leukotriene B4 / metabolism,  pharmacology
Neutrophils / metabolism
Receptors, Leukotriene B4 / antagonists & inhibitors*
Ricinoleic Acids / pharmacology
Swine
Tritium
Chemical
Reg. No./Substance:
0/Fatty Acids, Essential; 0/Fatty Acids, Unsaturated; 0/Receptors, Leukotriene B4; 0/Ricinoleic Acids; 10028-17-8/Tritium; 141-22-0/ricinoleic acid; 71160-24-2/Leukotriene B4; 7324-41-6/8,11,14-Eicosatrienoic Acid; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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