Document Detail


Chemical requirements for inhibition of gap junction communication by the biologically active lipid oleamide.
MedLine Citation:
PMID:  9560184     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oleamide is an endogenous fatty acid primary amide that possesses sleep-inducing properties in animals and has been shown to effect serotonergic systems and block gap junction communication in a structurally specific manner. Herein, the structural features of oleamide required for inhibition of the gap junction-mediated chemical and electrical transmission in rat glial cells are defined. The effective inhibitors fall into two classes of fatty acid primary amides of which oleamide and arachidonamide are the prototypical members. Of these two, oleamide constitutes the most effective, and its structural requirements for inhibition of the gap junction are well defined. It requires a chain length of 16-24 carbons of which 16-18 carbons appears optimal, a polarized terminal carbonyl group capable of accepting but not necessarily donating a hydrogen bond, a Delta9 cis double bond, and a hydrophobic methyl terminus. Within these constraints, a range of modifications are possible, many of which may be expected to improve in vivo properties. A select set of agents has been identified that serves both as oleamide agonists and as inhibitors of fatty acid amide hydrolase, which is responsible for the rapid inactivation of oleamide.
Authors:
D L Boger; J E Patterson; X Guan; B F Cravatt; R A Lerner; N B Gilula
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  95     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1998 Apr 
Date Detail:
Created Date:  1998-06-04     Completed Date:  1998-06-04     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4810-5     Citation Subset:  IM    
Affiliation:
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. boger@scripps.edu
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MeSH Terms
Descriptor/Qualifier:
Amidohydrolases / metabolism
Animals
Cell Communication / drug effects*
Cells, Cultured
Gap Junctions / drug effects*
Isomerism
Neuroglia / drug effects
Oleic Acids / chemistry,  metabolism,  pharmacology*
Rats
Structure-Activity Relationship
Grant Support
ID/Acronym/Agency:
CA42056/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Oleic Acids; 301-02-0/oleylamide; EC 3.5.-/Amidohydrolases; EC 3.5.1.-/fatty-acid amide hydrolase
Comments/Corrections

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


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