PROSTAGLANDIN UPTAKE AND CATABOLISM BY THE CHOROID-PLEXUS DURING DEVELOPMENT IN SHEEP

We have previously reported that prostaglandin(PG) E-2 levels in sheep cerebrospinal fluid (CSF) are high prenatally and abate rapidly after birth. This event may contribute to the establishment of continuous b reathing. To explain this change, we have examined PG disposal mechani sms in the perinatal and adult (pregnant and non-pregnant animal) shee p brain by measuring the capacity of the isolated choroid plexus to co ncentrate [H-3]PGF(2 alpha) and [H-3]PGE(2). At 0.9 gestation, [H-3]PG F(2 alpha) uptake (expressed as the tissue-to-medium ratio, T/M) attai ned a steady-state by 15 min and was maintained thereafter (T/M at 60 min, 5.6 +/- 0.6; n = 16), Likewise, [H-3]PGE(2) was taken up by the t issue, but the actual accumulation was smaller (T/M at 60 min, 2.6 +/- 0.2; n = 8). Thin-layer radiochromatographic analysis of the tissue f ollowing incubation with [H-3]PGF(2 alpha) showed that 55 +/- 4% (n = 10) of radioactivity migrated as the 15-keto-13,14-dihydro metabolite. [H-3]PGF(2 alpha) uptake decreased upon treatment with probenecid (1 mM) (T/M, 2.5 +/- 0.2; n = 10) or after adding unlabelled PGF(2 alpha) to the medium (1-60 mu M) (T/M at 60 mu M, 1.8 +/- 0.1; n = 13), The yield of labelled metabolite was also lower when using excess PGF(2 al pha) (14% of control at 60 mu M; n = 13), while it was not affected by probenecid, Uptake of both PGs did not change through development, fr om 0.7 gestation to day 18 postnatal, and attained higher values in th e pregnant adult. Conversely, PGF(2 alpha) catabolism decreased postna tally and became negligible by adult age. We conclude that during the perinatal period PGs can be removed from CSF by two distinct processes in the choroid plexus, active transport and catabolism. Neither proce ss, however, can account for the birth-related change in CSF PGE(2).