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  • 标题:Enzymatic formation of prostamide F2{alpha} from anandamide involves a newly identified intermediate metabolite, prostamide H2
  • 本地全文:下载
  • 作者:Yang, Wu ; Ni, Jinsong ; Woodward, David F.
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:2005
  • 卷号:46
  • 期号:12
  • 页码:2745-2751
  • DOI:10.1194/jlr.M500374-JLR200
  • 出版社:American Society for Biochemistry and Molecular Biology
  • 摘要:Prostaglandin F2{alpha} 1-ethanolamide (prostamide F2{alpha}) is a potent ocular hypotensive agent in animals and represents a new class of fatty acid amide compounds. Accumulated evidence indicated that anandamide, an endogenous bioactive ligand for cannabinoid receptors, may serve as a common substrate to produce all prostamides, including prostamide F2{alpha}. After incubation of anandamide with cyclooxygenase 2 (COX-2), the reaction mixture was profiled by HPLC and an intermediate metabolite was discovered and characterized as a cyclic endoperoxide ethanolamide using HPLC-tandem mass spectrometry. Formation of prostamide F2{alpha} was also demonstrated when the intermediate metabolite was isolated and incubated with prostaglandin F synthase (PGF synthase). These results suggest that the biosynthesis of prostamide F2{alpha} proceeds in two consecutive steps: oxidation of anandamide to form an endoperoxide intermediate by COX-2, and reduction of the endoperoxide intermediate to form prostamide F2{alpha} by PGF synthase. This endoperoxide ethanolamide intermediate has been proposed as prostamide H2. Supplementary key words cyclooxygenase 2 • prostaglandin F2{alpha} 1-ethanolamide • prostaglandin F synthase
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