Document Detail

Chemical requirements for inhibition of gap junction communication by the biologically active lipid oleamide.
MedLine Citation:
PMID:  9560184     Owner:  NLM     Status:  MEDLINE    
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.
D L Boger; J E Patterson; X Guan; B F Cravatt; R A Lerner; N B Gilula
Related Documents :
1263204 - Syntheses of heterocylic fused thiazole acetic acids. 2.
16391944 - Heterocyclic zinc-binding groups for use in next-generation matrix metalloproteinase in...
8292264 - Secondary fungal metabolites and their biological activities, iv. synthesis of compound...
12873484 - Pyrimidinone antibiotics--heterocyclic analogues with improved antibacterial spectrum.
11514074 - Phospholipid fatty acids and neurotoxicity in human neuroblastoma sh-sy5y cells.
20172724 - Ethacrynic acid analogues lacking the alpha,beta-unsaturated carbonyl unit--potential a...
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    
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Amidohydrolases / metabolism
Cell Communication / drug effects*
Cells, Cultured
Gap Junctions / drug effects*
Neuroglia / drug effects
Oleic Acids / chemistry,  metabolism,  pharmacology*
Structure-Activity Relationship
Grant Support
Reg. No./Substance:
0/Oleic Acids; 301-02-0/oleylamide; EC 3.5.-/Amidohydrolases; EC 3.5.1.-/fatty-acid amide hydrolase

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

Previous Document:  Second-order correction to the Bigeleisen-Mayer equation due to the nuclear field shift.
Next Document:  Engineering analysis of biological variables: an example of blood pressure over 1 day.