Profiles of prostaglandin metabolites in the human circulation. Identification of late-appearing, long-lived products.

The pattern of metabolites appearing in the circulation after intravenous injection of [9 beta-3H]prostaglandin F2 alpha was investigated in the human. Analysis of profiles of products was performed by two-dimensional TLC and autoradiography. Identification of labeled metabolites was accomplished by comparing their chromatographic behaviour with reference compounds in several chromatographic systems. After injection of [9 beta-3H]prostaglandin F2 alpha the initially formed metabolite was 15-keto-13,14-dihydroprostaglandin F2 alpha. However, this compound only dominated the spectrum of metabolites during the first few minutes, and several more polar products soon appeared. About 20 min after the injection the most prominent metabolite was 5 alpha, 7 alpha-dihydroxy-11-ketotetranorprostane-1,16-dioic acid, which remained the dominating plasma compound and was also the major metabolite in urine. Several other highly oxidized products were also identified in plasma. Also these metabolites appeared later and remained longer in the circulation than the initially formed 15-ketodihydro metabolite. Our findings suggested that the more degraded metabolites might serve as more reliable plasma parameters for monitoring prostaglandin production than the traditional parameter, 15-ketodihydroprostaglandin F2 alpha. This hypothesis was supported by radioimmunoassay of metabolite levels in plasma appearing after either exogenous (intravenous administration) or endogenous prostaglandin F2 alpha (late human pregnancy and parturition). In all cases studied, the tetranor metabolites remained elevated in the circulation for several hours, in contrast to their precursor, 15-ketodihydroprostaglandin F2 alpha, which disappeared rapidly.