title: The biosynthesis of N-arachidonoyl dopamine (NADA), a putative endocannabinoid and endovanilloid, via conjugation of arachidonic acid with dopamine.
abstract: 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.
authors: Department of Psychological and Brain Sciences and the Gill Center for Biomolecular Science, Indiana University, Bloomington, IN 47405, USA.
authors: Sherry Shu-Jung
authors: SS
authors: Hu
authors: Heather B
authors: HB
authors: Bradshaw
authors: Valery M
authors: VM
authors: Benton
authors: Jay Shih-Chieh
authors: JS
authors: Chen
authors: Susan M
authors: SM
authors: Huang
authors: Alberto
authors: A
authors: Minassi
authors: Tiziana
authors: T
authors: Bisogno
authors: Kim
authors: K
authors: Masuda
authors: Bo
authors: B
authors: Tan
authors: Robert
authors: R
authors: Roskoski
authors: Benjamin F
authors: BF
authors: Cravatt
authors: Vincenzo
authors: V
authors: Di Marzo
authors: J Michael
authors: JM
authors: Walker
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry / Q000378:metabolism*; D001095:Arachidonic Acids / Q000096:biosynthesis* / Q000737:chemistry; D001921:Brain / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000096:biosynthesis* / Q000737:chemistry; D004298:Dopamine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D063388:Endocannabinoids; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D016718:Arachidonic Acid; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D004298:Dopamine; D063388:Endocannabinoids; D000099252:Fatty Acid Amide Hydrolases; C474941:arachidonyl dopamine