Differential uptake and catabolism of prostaglandin (PG)E-2 versus PGF(2 alpha) in the sheep choroid plexus during development

The early postnatal decrease in prostaglandin (PG)E-2 levels in cerebrospin al fluid (CSF) likely contributes to the establishment of continuous breath ing. To elucidate mechanisms underlying this event, choroid plexuses from l ateral (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 mea sured. [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 t he pregnant adult. Release of the two compounds was similar and did not cha nge with age. [H-3]-PGE(2) uptake was reduced by probenecid (1 mM) and exce ss PG (60 mu M PGE(2) or PGF(2 alpha)). Excess PG also reduced catabolism i n the fetus, which was extensive for [H-3]-PGE(2) and [H-3]-PGF(2 alpha) un der 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 no t [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 catabo lism was reduced by probenecid. In conclusion, PGE, uptake and catabolism o perate independently in the choroid plexus from perinatal sheep. Difference s between PGE(2) and PGF(2 alpha) are developmentally-regulated for both me chanisms. 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.