出版社:American Society for Biochemistry and Molecular Biology
摘要:Prostaglandin F2 1-ethanolamide (prostamide F2) is a potentocular hypotensive agent in animals and represents a new classof fatty acid amide compounds. Accumulated evidence indicatedthat anandamide, an endogenous bioactive ligand for cannabinoidreceptors, may serve as a common substrate to produce all prostamides,including prostamide F2. After incubation of anandamide withcyclooxygenase 2 (COX-2), the reaction mixture was profiledby HPLC and an intermediate metabolite was discovered and characterizedas a cyclic endoperoxide ethanolamide using HPLC-tandem massspectrometry. Formation of prostamide F2 was also demonstratedwhen the intermediate metabolite was isolated and incubatedwith prostaglandin F synthase (PGF synthase).
These results suggest that the biosynthesis of prostamide F2proceeds in two consecutive steps: oxidation of anandamide toform an endoperoxide intermediate by COX-2, and reduction ofthe endoperoxide intermediate to form prostamide F2 by PGF synthase.This endoperoxide ethanolamide intermediate has been proposedas prostamide H2.Supplementary key words cyclooxygenase 2 • prostaglandin F2 1-ethanolamide • prostaglandin F synthase