The biosynthesis of N-arachidonoyl dopamine (NADA), a putative endocannabinoid and endovanilloid, via conjugation of arachidonic acid with dopamine

Sherry Shu Jung Hu, Heather B. Bradshaw, Valery M. Benton, Jay Shih Chieh Chen, Susan M. Huang, Alberto Minassi, Tiziana Bisogno, Kim Masuda, Bo Tan, Robert Roskoski, Benjamin F. Cravatt, Vincenzo Di Marzo, J. Michael Walker

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61 引文 斯高帕斯(Scopus)

摘要

N-arachidonoyl dopamine (NADA) is an endogenous ligand that activates the cannabinoid type 1 receptor and the transient receptor potential vanilloid type 1 channel. Two potential biosynthetic pathways for NADA have been proposed, though no conclusive evidence exists for either. The first is the direct conjugation of arachidonic acid with dopamine and the other is via metabolism of a putative N-arachidonoyl tyrosine (NA-tyrosine). In the present study we investigated these biosynthetic mechanisms and report that NADA synthesis requires TH in dopaminergic terminals; however, NA-tyrosine, which we identify here as an endogenous lipid, is not an intermediate. We show that NADA biosynthesis primarily occurs through an enzyme-mediated conjugation of arachidonic acid with dopamine. While this conjugation likely involves a complex of enzymes, our data suggest a direct involvement of fatty acid amide hydrolase in NADA biosynthesis either as a rate-limiting enzyme that liberates arachidonic acid from AEA, or as a conjugation enzyme, or both.

原文English
頁(從 - 到)291-301
頁數11
期刊Prostaglandins Leukotrienes and Essential Fatty Acids
81
發行號4
DOIs
出版狀態Published - 2009 10月

All Science Journal Classification (ASJC) codes

  • 臨床生物化學
  • 細胞生物學

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