Premium
Metabolism of Prostaglandin D 2 by Human Cerebral Cortex into 9α, 11β‐Prostaglandin F 2 by an Active NADPH‐Dependent 11‐Ketoreductase
Author(s) -
Wolfe L. S.,
Rostworowski K.,
Pellerin L.,
Sherwin A.
Publication year - 1989
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1989.tb07295.x
Subject(s) - prostaglandin , cerebral cortex , incubation , metabolism , cortex (anatomy) , neocortex , endocrinology , medicine , microsome , chemistry , cytosol , prostaglandin e , arachidonic acid , human brain , pathophysiology , biochemistry , biology , enzyme , neuroscience
In homogenates of rat cerebral neocortex prostaglandin D 2 (PGD 2 ) 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 PGD 2 (4.5–11.7 ng/g wet weight/30 min) were formed. Furthermore, PGD 2 , added to homogenates of human biopsy temporal cortex, was converted efficiently into 9α,11β‐PGF 2 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‐PGF 2 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 PGD 2 found in incubations of human brain tissue. The rat brain does not contain 11‐ketoreductase activity. The present results indicate that the 9α, 11β‐PGF 2 must be considered along with other eicosanoids in pathophysiological situations in brain.