Transport of prostaglandins across the blood-brain and blood-aqueons barriers and the physiological significance of these absorptive transport processes

Abstract

Prostaglandins (PGs) are accumulated in vitro against an apparent concentration gradient by some vertebrate tissues including the choroid plexuses and the anterior uvea of all species studied. This concentrative accumulation is saturable and can be inhibited by organic acid transport inhibitors, such as probenecid and bromcresol green. In vivo experiments show that loss of PGs from the extracellular fluids of the brain and the eye is dependent on saturable, carrier-mediated, transport processes which are also affected by the same inhibitors. Such facilitated removal of PGs across the blood-brain and blood-ocular barriers appears to be the major mechanism for the termination of action of these potent autacoids which are produced but are not effectively metabolized by brain and intraocular tissues. The apparent physiological significance of these PG transport processes was demonstrated experimentally by showing that application of 8/µg PGE 1 but not PGF 2α , over the visual cortex caused inhibition and alteration of the visually evoked response and induction of epileptiform activity only in rabbits which were pretreated with known inhibitors of PG transpoit. Pretreatment with PG transport inhibitors also enhanced the hyperthermic effects of PGE 1 , PGE 2 and PGF 2α . The effects of intravitreally injected PGE 1 on the electrical activity of the retina and the visual cortex were also enhanced by pretreatment with bromcresol green. Pretreatment with PG transport inhibitors decreased the loss of intravitreally injected [ 3 H]PGF 2α from the vitreous, and increased its accumulation in the aqueous. The ability of the iris-ciliary body complex to accumulate PGs in vitro and thus, presumably, its ability to remove PGs from the intraocular fluids in vivo, was found to be severely decreased during the course of inflammation, and even several months following an episode of severe uveitis. Since PGs can have a potentially adverse effect on the brain and the eye, when allowed to accumulate to abnormal levels, inhibition of these transport processes by drugs or as a sequelae of pathological conditions may account for some effects or side effects of such drugs and for the recurrent nature of uveitis and epileptic seizures.