Document Detail


A possible role of lipoxygenase in the activation of vanilloid receptors by anandamide in the guinea-pig bronchus.
MedLine Citation:
PMID:  11522594     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. In the absence of indomethacin, anandamide did not contract the guinea-pig bronchus at concentrations up to 100 microM. In the presence of indomethacin (10 microM), anandamide induced concentration-related contractions with a pEC(50) value of 5.18+/-0.11. It was significantly less potent than capsaicin (pEC(50) 7.01+/-0.1). The anandamide uptake inhibitor AM404, produced only a 14.1+/-3.22% contraction at 100 microM. All experiments were conducted in the presence of PMSF (20 microM). 2. The vanilloid receptor antagonist, capsazepine (10 microM), significantly attenuated the contractile effect of anandamide, the response to 100 microM anandamide being 40.53+/-7.04% in the presence of vehicle and 1.57+/-8.93% in the presence of 10 microM capsazepine. The contractile actions of anandamide and AM404 were markedly enhanced by the peptidase inhibitor thiorphan. 3. The log concentration-response curve of anandamide was unaltered by the CB1 receptor antagonist, SR141716A. The pEC(50) values for anandamide were 4.88+/-0.08 and 5.17+/-0.19 in the presence of vehicle and SR141716A (1 microM) respectively. 4. The lipoxygenase inhibitors 5,8,11,14-eicosatetraynoic acid (ETYA) and 5,8,11 eicosatriynoic acid (ETI) reduced the effect of 100 microM anandamide from 34.7+/-1.9% (vehicle) to 7.7+/-5% (ETYA, 10 microM) and from 41.85+/-4.25% (n=6) (vehicle) to 10.31+/-3.54 (n=6) (ETI, 20 microM). Neither inhibitor significantly affected contraction of the tissue by substance P. 5. This study provides evidence that anandamide acts on vanilloid receptors in the guinea-pig isolated bronchus. These data raise the possibility that the contractile action of anandamide may be due, at least in part, to lipoxygenase metabolites of this fatty acid amide that are vanilloid receptor agonists.
Authors:
S J Craib; H C Ellington; R G Pertwee; R A Ross
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  British journal of pharmacology     Volume:  134     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2001 Sep 
Date Detail:
Created Date:  2001-08-27     Completed Date:  2001-10-11     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  30-7     Citation Subset:  IM    
Affiliation:
Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, Scotland, UK.
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MeSH Terms
Descriptor/Qualifier:
5,8,11,14-Eicosatetraynoic Acid / pharmacology
Animals
Arachidonic Acids / pharmacology*
Bronchi / drug effects*,  physiology
Calcium Channel Blockers / pharmacology*
Capsaicin / analogs & derivatives*,  pharmacology
Cyclohexanols / pharmacology
Dose-Response Relationship, Drug
Endocannabinoids
Fatty Acids, Unsaturated / pharmacology
Guinea Pigs
Hydrazines / pharmacology
Indomethacin / pharmacology
Lipoxygenase / drug effects,  physiology*
Muscle Contraction / drug effects
Oxazepines / pharmacology
Piperidines / pharmacology
Polyunsaturated Alkamides
Pyrazoles / pharmacology
Receptors, Drug / drug effects*,  metabolism
Thiorphan / pharmacology
Chemical
Reg. No./Substance:
0/Arachidonic Acids; 0/Calcium Channel Blockers; 0/Cyclohexanols; 0/Endocannabinoids; 0/Fatty Acids, Unsaturated; 0/Hydrazines; 0/Oxazepines; 0/Piperidines; 0/Polyunsaturated Alkamides; 0/Pyrazoles; 0/Receptors, Drug; 1191-85-1/5,8,11,14-Eicosatetraynoic Acid; 13488-22-7/5,8,11-eicosatriynoic acid; 146033-02-5/SC 51089; 158681-13-1/rimonabant; 404-86-4/Capsaicin; 53-86-1/Indomethacin; 76721-89-6/Thiorphan; 83003-12-7/3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; 94421-68-8/anandamide; EC 1.13.11.12/Lipoxygenase; LFW48MY844/capsazepine
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