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

Abstract 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 [ 3 H ]-PGE 2 and label uptake (tissue-to-medium ratio for radioactivity, T/M) and catabolism (%radioactivity associated with metabolites, PGM) were measured. [ 3 H ]-PGF 2α was a reference. Uptake of [ 3 H ]-PGE 2 was lower than [ 3 H ]-PGF 2α 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. [ 3 H ]-PGE 2 uptake was reduced by probenecid (1 mM) and excess PG (60 μM PGE 2 or PGF 2α ). Excess PG also reduced catabolism in the fetus, which was extensive for [ 3 H ]-PGE 2 and [ 3 H ]-PGF 2α under basal conditions (PGM>60%). In the lamb, catabolism remained high for [ 3 H ]-PGE 2 (L-CP: 64±4%, n =7; III/IV-CP: 41±4%, n =3), but not [ 3 H ]-PGF 2α (L-CP: 26±4%, n =7; III/IV-CP: 4±1%, n =4). In the pregnant adult, catabolism was above background only for [ 3 H ]-PGE 2 in the L-CP (26±5%, n =11). Unlike the perinatal animal, this catabolism was reduced by probenecid. In conclusion, PGE 2 uptake and catabolism operate independently in the choroid plexus from perinatal sheep. Differences between PGE 2 and PGF 2α 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.