Metabolism of prostaglandin D2 in the monkey

• Published in: The Journal of biological chemistry 1979-05, Vol.254 (10), p.4152-4163
• Main Authors: Ellis, C K, Smigel, M D, Oates, J A, Oelz, O, Sweetman, B J
• Format: Article
• Language: English
• Subjects: Animals; Arachidonic Acids - metabolism; Blood Pressure - drug effects; Chromatography, Gas; Haplorhini; Heart Rate - drug effects; Male; Mass Spectrometry; Microsomes - metabolism; Prostaglandins - metabolism; Prostaglandins D - metabolism; Prostaglandins D - pharmacology; Seminal Vesicles - metabolism; Sheep
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)50709-2

[3H7]Prostaglandin D2 was biosynthesized and infused into an unanesthetized monkey. The urinary metabolites were isolated and subsequently identified by gas chromatography-mass spectrometry. Two pathways of prostaglandin D2 metabolism were identified and resulted in metabolites with prostaglandin D (3-hydroxycyclopentanone) and prostaglandin F (cyclopentane-1,3-diol) ring structures. The major prostaglandin D ring metabolite was identified as 9,20-dihydroxy-11,15-dioxo-2,3-dinorprost-5-en-1-oic acid. Nine other prostaglandin D ring metabolites were identified reflecting various combinations of metabolism by beta and omega oxidation, 15 dehydrogenation, and 13-14 reduction. In greater abundance were those prostaglandin D2 metabolites which had the prostaglandin F ring structure. The major prostaglandin D2 metabolite which had the prostaglandin F ring structure was identified as 9,11,15-trihydroxy-2,3-dinorprosta-5,13-dien-1-oic acid (dinor prostaglandin F2 alpha). Nine other metabolites with the prostaglandin F ring structure were identified, including prostaglandin F2 alpha itself. These, for the most part, were the structural counterparts of the metabolites with the prostaglandin D ring. Since many prostaglandin D2 metabolites were found to be identical with the metabolites of prostaglandin F2 alpha, quantitative determinations of prostaglandin F ring metabolites may not be a specific indicator of prostaglandin F2 alpha biosynthesis. Likewise, data involving the measurement of a biological effect of prostaglandin D2 must be re-examined to account for the possible contribution of prostaglandin F2 alpha, a metabolite of prostaglandin D2, to the biological response.