Metabolism of Prostaglandin D2 by Human Cerebral Cortex into 9α, 11β-Prostaglandin F2 by an Active NADPH-Dependent 11-Ketoreductase

Abstract: In homogenates of rat cerebral neocortex prostaglandin D₂ (PGD₂) was found to be quantitatively the main PG biosynthesized by a cytosolic PGD synthetase from en-dogenously released arachidonic acid. Amounts of 628 ng/g wet weight were found after 30-min incubation periods compared with basal levels of 2.3 ng/g wet weight. In human cerebral cortex, whether obtained at biopsy or postmortem, only small amounts of PGD₂ (4.5–11.7 ng/g wet weight/30 min) were formed. Furthermore, PGD₂, added to homogenates of human biopsy temporal cortex, was converted efficiently into 9α,11β-PGF₂ by a NADPH-dependent 11-ke-toreductase as has been reported in other human tissues (liver and lung). PGF_2α was determined directly as the fl-butylbo-ronate derivative. It became clear that 9α,11β-PGF₂ was formed in considerably greater amounts than PGF_2α and that other metabolites are also formed. These results can account for the low amounts of PGD₂ found in incubations of human brain tissue. The rat brain does not contain 11-ketoreductase activity. The present results indicate that the 9α, 11β-PGF₂ must be considered along with other eicosanoids in pathophysiological situations in brain.