Hiroyoshi Osama

Changes of enzymes involved in prostaglandin metabolism and prostaglandin binding proteins in rat brain during development and aging.

Abstract: In the developing rat brain, the enzymatic formation of prostaglandin D2 from prostaglandin H2 increased 60‐fold from day 12 of gestation to birth. The activity still rose gradually to the highest level (90 nmol/min/g wet tissue) at day 7 after birth. The activities of prostaglandin E2 and F2α synthetases in rat brain were highest at gestational age 19 days (30 nmol/min/g wet tissue) and at gestational age 14 days (15 nmol/min/g wet tissue), respectively. The specific activity of NADP‐dependent 15‐hydroxy‐prostaglandin D2 dehydrogenase in rat brain was highest at the earliest gestational age we examined (day 12 of gestation), The specific bindings of prostaglandin D2 and E2 to the crude mitochondrial fraction of rat brain were observed from day 16 of gestation and increased to day 7 after birth. Although the activities of the enzymes responsible for prostaglandin metabolism were unchanged postmaturationally, the maximal concentrations of the binding sites on the synaptic membrane for both prostaglandins D2 and E2 decreased with constant affinity to less than one‐sixth with age from 1 week to 24 months after birth. These results indicate that prostaglandins may play important roles during maturation and aging in rat brain.

Suppression of sleep by prostaglandin synthesis inhibitors in unrestrained rats

Sleep-suppressive activity of prostaglandin synthesis inhibitors, diclofenac sodium (DF) and indomethacin (IM), was examined in unrestrained male rats. An intraperitoneal injection of 5 mg/kg IM, or an oral administration of 5 mg/kg DF and 10 mg/kg IM at an early phase of the light period transiently decreased slow wave sleep (SWS) and paradoxical sleep (PS) to 30-62% and 0-38%, respectively, of the control level in the first hour. An intravenous infusion of 0.4 mg DF or 0.4 mg IM or an intracerebroventricular infusion of 0.04 mg DF continuously during a 10-h diurnal period resulted in a significant decrease in SWS and PS by 9-17% and 17-21%, respectively, from the baseline value in the 12-h light period. The DF infusion was accompanied by a rebound rise in the nocturnal SWS and PS and the subsequent diurnal PS. The results indicate that the depletion of prostaglandin(s) in the brain is responsible for the DF- and IM-induced suppression of sleep.