| Inhibition of anandamide hydrolysis by the enantiomers of ibuprofen, ketorolac, and flurbiprofen. | |
| | |
MedLine Citation:
|
PMID: 9989926 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The endogenous cannabimimetic anandamide is hydrolyzed by a fatty acid amide hydrolase to yield arachidonic acid and ethanolamine. In the present study, the regional distribution of the activity and its sensitivity to inhibition by the enantiomers of ibuprofen, ketorolac, and flurbiprofen has been investigated. The rate of [3H]anandamide hydrolysis was found in both 7-week-old and 90-week-old rats to be in the order hippocampus > cerebral cortex > cerebellum > striatum approximately midbrain, with higher rates of hydrolysis for the 7-week-old rats than for the 90-week-old rats. In whole brain (minus cerebellum), the R(-)-enantiomer of ibuprofen was a mixed-type inhibitor of anandamide hydrolysis and was approximately 2-3 times more potent than the S(+)-enantiomer, IC50 values of 230 and 750 microM, respectively, being found. A similar pattern of inhibition of anandamide hydrolysis was seen when intact C6 rat glioma cells were used. Ketorolac inhibited rat brain anandamide hydrolysis, with IC50 values of 50, 440, and 80 microM being found for the R-, S-, and R,S-forms, respectively. The IC50 value for R-flurbiprofen (60 microM) was similar to the IC50 value for the S-enantiomer (50 microM). These data demonstrate that there is no dramatic enantiomeric selectivity of NSAID compounds as inhibitors of fatty acid amide hydrolase enzyme(s) responsible for the hydrolysis of anandamide. The enantiomers of flurbiprofen and R-ketorolac are the most potent NSAID inhibitors of fatty acid amide hydrolase yet reported. |
| | |
Authors:
|
C J Fowler; U Janson; R M Johnson; G Wahlström; A Stenström; K Norström; G Tiger |
Related Documents
:
|
1968336 - Detection of 2h-1,4-thiazine-5,6-dihydro-3-carboxylic acid (aminoethylcysteine ketimine... 7390716 - Regional brain ascorbic acid distribution: its functional relationship to appetite and ... 9928896 - Streptozotocin increases free fatty acids and decreases phospholipids in rat brain. 12235226 - Manipulation of brain kynurenines: glial targets, neuronal effects, and clinical opport... 6088546 - Substrate specificities of active transport systems for amino acids in vacuolar-membran... 9845426 - Diagnosis and interpretation of steatosis and steatohepatitis. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Archives of biochemistry and biophysics Volume: 362 ISSN: 0003-9861 ISO Abbreviation: Arch. Biochem. Biophys. Publication Date: 1999 Feb |
Date Detail:
|
Created Date: 1999-03-11 Completed Date: 1999-03-11 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0372430 Medline TA: Arch Biochem Biophys Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 191-6 Citation Subset: IM |
Copyright Information:
|
Copyright 1999 Academic Press. |
Affiliation:
|
Department of Pharmacology, Umeå University, Sweden. cf@pharm.umu.se |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aging Animals Arachidonic Acids / metabolism* Brain / drug effects*, metabolism, pathology Cell Extracts Cell Survival / drug effects Dose-Response Relationship, Drug Flurbiprofen / analogs & derivatives, pharmacology* Glioma Hydrolysis / drug effects Ibuprofen / analogs & derivatives, pharmacology* Inhibitory Concentration 50 Ketorolac Kinetics Polyunsaturated Alkamides Rats Rats, Sprague-Dawley Stereoisomerism Time Factors Tolmetin / analogs & derivatives*, pharmacology Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
|
0/Arachidonic Acids; 0/Cell Extracts; 0/Polyunsaturated Alkamides; 15687-27-1/Ibuprofen; 26171-23-3/Tolmetin; 5104-49-4/Flurbiprofen; 66635-83-4/Ketorolac; 94421-68-8/anandamide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Flavor preferences conditioned by intragastric nutrient infusions in rats fed chow or a cafeteria di...
Next Document: Activation of the P2Z/P2X7 receptor in human lymphocytes produces a delayed permeability lesion: inv...