Differential uptake and catabolism of prostaglandin (PG)E2 versus PGF2α in the sheep choroid plexus during development

The early postnatal decrease in prostaglandin (PG)E-2 levels in cerebrospinal fluid (CSF) likely contributes to the establishment of continuous breathing. To elucidate mechanisms underlying this event, choroid plexuses from lateral (L-CP) and third/fourth (III/IV-CP) ventricles were incubated with [H-3]-PGE(2) and label uptake (tissue-to-medium ratio for radioactivity, T/M) and catabolism (%radioactivity associated with metabolites, PGM) were measured. [H-3]-PGF(2 alpha) was a reference. Uptake of [H-3]-PGE(2) was lower than [H-3]-PGF(2 alpha) in the term fetus (L-CP: 5.9 +/- 0.5 vs. 9.6 +/- 0.9, n = 11; III/IV-CP: 2.7 +/-0.4 vs. 7.7 +/- 1.0, n = 5) and 17 d lamb (L-CP: 5.3 +/- 0.8 vs. 11.0 +/- 1.2, n = 7; III/IV-CP: 3.1 +/- 0.2 vs. 11.6 +/- 2.8, n = 3 and 4, respectively). This difference was not significant in the pregnant adult. Release of the two compounds was similar and did not change with age. [H-3]-PGE(2) uptake was reduced by probenecid (1 mM) and excess PG (60 mu M PGE(2) or PGF(2 alpha)). Excess PG also reduced catabolism in the fetus, which was extensive for [H-3]-PGE(2) and [H-3]-PGF(2 alpha) under basal conditions (PGM > 60%). In the lamb, catabolism remained high for [H-3]-PGE(2) (L-CP: 64 +/- 4%, n = 7; III/IV-CP: 41 +/- 4%, n = 3), but not [H-3]-PGF(2 alpha) (L-CP: 26 +/- 4%, n = 7; III/IV-CP: 4 +/- 1%, n = 4). In the pregnant adult, catabolism was above background only for [H-3]-PGE(2) in the L-CP (26 +/- 5%, n = 11). Unlike the perinatal animal, this catabolism was reduced by probenecid. In conclusion, PGE, uptake and catabolism operate independently in the choroid plexus from perinatal sheep. Differences between PGE(2) and PGF(2 alpha) are developmentally-regulated for both mechanisms. While neither process explains the postnatal decrease in CSF PGE(2), both may help keep CSF levels low during early postnatal development. (C) 2000 Elsevier Science B.V. All rights reserved.