title: Identification of a new class of molecules, the arachidonyl amino acids, and characterization of one member that inhibits pain.
abstract: In mammals, specific lipids and amino acids serve as crucial signaling molecules. In bacteria, conjugates of lipids and amino acids (referred to as lipoamino acids) have been identified and found to possess biological activity. Here, we report that mammals also produce lipoamino acids, specifically the arachidonyl amino acids. We show that the conjugate of arachidonic acid and glycine (N-arachidonylglycine (NAGly)) is present in bovine and rat brain as well as other tissues and that it suppresses tonic inflammatory pain. The biosynthesis of NAGly and its degradation by the enzyme fatty acid amide hydrolase can be observed in rat brain tissue. In addition to NAGly, bovine brain produces at least two other arachidonyl amino acids: N-arachidonyl gamma-aminobutyric acid (NAGABA) and N-arachidonylalanine. Like NAGly, NAGABA inhibits pain. These findings open the door to the identification of other members of this new class of biomolecules, which may be integral to pain regulation and a variety of functions in mammals.
authors.affiliation: Department of Psychology, Brown University, Providence, Rhode Island 02912, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Huang
authors.forename: T
authors.initials: T
authors.lastname: Bisogno
authors.forename: T J
authors.initials: TJ
authors.lastname: Petros
authors.forename: S Y
authors.initials: SY
authors.lastname: Chang
authors.forename: P A
authors.initials: PA
authors.lastname: Zavitsanos
authors.forename: R E
authors.initials: RE
authors.lastname: Zipkin
authors.forename: R
authors.initials: R
authors.lastname: Sivakumar
authors.forename: A
authors.initials: A
authors.lastname: Coop
authors.forename: D Y
authors.initials: DY
authors.lastname: Maeda
authors.forename: L
authors.initials: L
authors.lastname: De Petrocellis
authors.forename: S
authors.initials: S
authors.lastname: Burstein
authors.forename: V
authors.initials: V
authors.lastname: Di Marzo
authors.forename: J M
authors.initials: JM
authors.lastname: Walker
mesh_terms: D000409:Alanine / Q000737:chemistry; D000581:Amidohydrolases / Q000378:metabolism; D000596:Amino Acids / Q000737:chemistry* / Q000145:classification*; D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry* / Q000145:classification*; D001095:Arachidonic Acids / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D005557:Formaldehyde / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005998:Glycine / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D010146:Pain / Q000188:drug therapy*; D053284:Polyunsaturated Alkamides; D011485:Protein Binding; D051381:Rats; D015398:Signal Transduction; D013997:Time Factors; D014018:Tissue Distribution; D005680:gamma-Aminobutyric Acid / Q000737:chemistry; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000409:Alanine; D000581:Amidohydrolases; D000596:Amino Acids; D016718:Arachidonic Acid; D001095:Arachidonic Acids; D002118:Calcium; D063388:Endocannabinoids; D005557:Formaldehyde; D005998:Glycine; D053284:Polyunsaturated Alkamides; D005680:gamma-Aminobutyric Acid; D000099252:Fatty Acid Amide Hydrolases; C078814:anandamide