Abstract

Incubation of 15-keto[ 3H] prostaglandin F 2α with glutathione (GSH) produced a metabolite of 15-keto-prostaglandin F 2α which was not extractable from aqueous solution and thus termed ‘water-soluble metabolite’. The addition of cytosol of guinea pig liver to the incubation mixture increased the formation of water soluble metabolite of 15-keto-prostaglandin F 2α 3-fold. The conversion of 15-keto-prostaglandin F 2α to water soluble metabolite in both the presence and absence of enzyme was linear during 10 min of incubation and required 2.5 mM GSH for maximal activity. Liver and kidney cytosol possess about 70 and 25 times, respectively, as much activity as compared to lung cytosol. Chromatographic analysis of the water soluble metabolite obtained from incubation of either 15-keto[ 3H] prostaglandin F 2α and GSH or [ 3H]GSH and 15-keto-prostaglandin F 2α showed that the water-soluble metabolite was an adduct of 15-keto-prostaglandin F 2α and GSH. The addition of prostaglandin A 1, a substrate of GSH S-transferases, to the incubation mixture competitively inhibited the formation of the water-soluble metabolite of 15-keto[ 3H] prostaglandin F 2α. Presumably, 15-keto-prostaglandin F 2α and other 15-keto-prostaglandins are converted to GSH conjugates by GSH S-transferases. This indicates that 15-keto-metabolites produced by prostaglandin dehydrogenase may be further metabolized to GSH conjugates.

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