Transport of prostaglandin D2 into brain

We examined the brain uptake of prostaglandin D2 after its i.v. administration to mice. The determination of this prostaglandin in tissues was performed by a sensitive and rapid radioimmunoassay after purification of the prostaglandin by high-performance liquid chromatography. When 1.0 mg/kg of prostaglandin D2 was injected, it was detectable in the brain 30 s after its administration (44 ng/g brain, about 0.08% of the administered dose). Brain uptake of prostaglandin D2 was dose-dependent over the dose range from 0.1 to 1.0 mg/kg and its half-life in the brain and blood was 1.1 and 0.9 min, respectively. The brain/blood ratio of the prostaglandin D2 concentration was 0.03 at 30 s and gradually increased to 0.2 during the first 15 min. These results suggest that prostaglandin D2 is taken up intact by the brain and disappears rapidly. Studies on the metabolic fate of tritium-labeled prostaglandin D2 revealed that it was a major component at 1 min, was metabolized to a number of hydrophilic and hydrophobic substances in the brain, whereas it was metabolized to mainly hydrophilic substances in the blood at 6 and 15 min, and the total radioactivities were cleared from the brain and blood with half-lives of 1.6 and 1.5 min, respectively.