Prostaglandin E2 metabolism in rat brain: Role of the blood-brain interfaces

The specific activity of 15-hydroxyprostaglandin dehydrogenase was measured in homogenates of microvessels, choroid plexuses and cerebral cortex isolated from postnatal and adult rat brain, and compared to the activity measured in peripheral organs which are established signal termination sites for prostaglandins. PGE2 metabolites produced ex vivo by choroid plexuses were identified and quantified by HPLC coupled to radiochemical detection.The data confirmed the absence of metabolic activity in brain parenchyma, and showed that no detectable activity was associated with brain microvessels forming the blood-brain barrier. By contrast, 15-hydroxyprostaglandin dehydrogenase activity was measured in both fourth and lateral ventricle choroid plexuses from 2-day-old rats, albeit at a lower level than in lung or kidney. The activity was barely detectable in adult choroidal tissue. Metabolic profiles indicated that isolated choroid plexus has the ability to metabolize PGE2, mainly into 13,14-dihydro-15-keto-PGE2. In short-term incubations, this metabolite distributed in the tissue rather than in the external medium, suggesting its release in the choroidal stroma.The rat choroidal tissue has a significant ability to metabolize PGE2 during early postnatal life. This metabolic activity may participate in signal termination of centrally released PGE2 in the brain, or function as an enzymatic barrier acting to maintain PGE2 homeostasis in CSF during the critical early postnatal period of brain development.Prostaglandin E2 (PGE2) is a main product of the cyclooxygenase (Cox) pathway. Two Cox isoenzymes, Cox-1 and Cox-2, convert arachidonic acid released by phospholipases A2 to PGH2, which in turn is metabolized by terminal prostaglandin E synthases into PGE2 [1]. While Cox-1 is constitutively expressed in most tissues where it fine-tunes physiological processes [2], Cox-2 expression is very limited in normal conditions in peripheral organs. Yet it is induced by inflammatory stimu