Document Detail

N-oleoyldopamine, a novel endogenous capsaicin-like lipid that produces hyperalgesia.
MedLine Citation:
PMID:  12569099     Owner:  NLM     Status:  MEDLINE    
N-Arachidonoyldopamine (NADA) was recently identified as an endogenous ligand for the vanilloid type 1 receptor (VR1). Further analysis of the bovine striatal extract from which NADA was isolated indicated the existence of substances corresponding in molecular mass to N-oleoyldopamine (OLDA), N-palmitoyldopamine (PALDA), and N-stearoyldopamine (STEARDA). Quadrupole time-of-flight mass spectrometric analysis of bovine striatal extracts revealed the existence of OLDA, PALDA, and STEARDA as endogenous compounds in the mammalian brain. PALDA and STEARDA failed to affect calcium influx in VR1-transfected human embryonic kidney (HEK) 293 cells or paw withdrawal latencies from a radiant heat source, and there was no evidence of spontaneous pain behavior. By contrast, OLDA induced calcium influx (EC(50) = 36 nm), reduced the latency of paw withdrawal from a radiant heat source in a dose-dependent manner (EC(50) = 0.72 microg), and produced nocifensive behavior. These effects were blocked by co-administration of the VR1 antagonist iodo-resiniferatoxin (10 nm for HEK cells and 1 microg/50 micro;l for pain behavior). These findings demonstrate the existence of an endogenous compound in the brain that is similar to capsaicin and NADA in its chemical structure and activity on VR1. Unlike NADA, OLDA was only a weak ligand for rat CB1 receptors; but like NADA, it was recognized by the anandamide membrane transporter while being a poor substrate for fatty-acid amide hydrolase. Analysis of the activity of six additional synthetic and potentially endogenous N-acyldopamine indicated the requirement of a long unsaturated fatty acid chain for an optimal functional interaction with VR1 receptors.
Constance J Chu; Susan M Huang; Luciano De Petrocellis; Tiziana Bisogno; Scott A Ewing; Jeffrey D Miller; Robert E Zipkin; Nives Daddario; Giovanni Appendino; Vincenzo Di Marzo; J Michael Walker
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2003-02-04
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  278     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-04-14     Completed Date:  2003-05-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13633-9     Citation Subset:  IM    
Department of Psychology, Brown University, Providence, Rhode Island 02912, USA.
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MeSH Terms
Arachidonic Acids / pharmacology
Brain / metabolism
Calcium / metabolism
Calcium Channel Blockers / pharmacology
Capsaicin / chemistry*,  pharmacology
Cell Line
Cell Membrane / metabolism
Cytosol / metabolism
Diterpenes / pharmacology
Dopamine / analogs & derivatives*,  chemistry,  pharmacology*
Dose-Response Relationship, Drug
Hyperalgesia / etiology*
Inhibitory Concentration 50
Mass Spectrometry
Models, Chemical
Polyunsaturated Alkamides
Protein Binding
Rats, Sprague-Dawley
Receptors, Drug / antagonists & inhibitors
TRPV Cation Channels
Time Factors
Grant Support
Reg. No./Substance:
0/Arachidonic Acids; 0/Calcium Channel Blockers; 0/Diterpenes; 0/Ions; 0/Lipids; 0/Polyunsaturated Alkamides; 0/Receptors, Drug; 0/TRPV Cation Channels; 0/iodoresiniferatoxin; 0/vanilloid receptor subtype 1; 404-86-4/Capsaicin; 7440-70-2/Calcium; 94421-68-8/anandamide

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

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