title: Differential uptake and catabolism of prostaglandin (PG)E(2) versus PGF(2alpha) 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 [3H]-PGE(2) and label uptake (tissue-to-medium ratio for radioactivity, T/M) and catabolism (%radioactivity associated with metabolites, PGM) were measured. [3H]-PGF(2alpha) was a reference. Uptake of [3H]-PGE(2) was lower than [3H]-PGF(2alpha) 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. [3H]-PGE(2) uptake was reduced by probenecid (1 mM) and excess PG (60 microM PGE(2) or PGF(2alpha)). Excess PG also reduced catabolism in the fetus, which was extensive for [3H]-PGE(2) and [3H]-PGF(2alpha)60%). In the lamb, catabolism remained high for [3H]-PGE(2) (L-CP: 64+/-4%, n=7; III/IV-CP: 41+/-4%, n=3), but not [3H]-PGF(2alpha) (L-CP: 26+/-4%, n=7; III/IV-CP: 4+/-1%, n=4). In the pregnant adult, catabolism was above background only for [3H]-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(2alpha) 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.
authors.affiliation: Integrative Biology Programme, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Krunic
authors.forename: S L
authors.initials: SL
authors.lastname: Adamson
authors.forename: F
authors.initials: F
authors.lastname: Coceani
mesh_terms: D000328:Adult; D000375:Aging / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002552:Cerebral Ventricles / Q000378:metabolism; D002831:Choroid Plexus / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D015237:Dinoprost / Q000378:metabolism* / Q000493:pharmacokinetics*; D015232:Dinoprostone / Q000378:metabolism* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D011247:Pregnancy; D011339:Probenecid / Q000494:pharmacology; D012756:Sheep; D014528:Uricosuric Agents / Q000494:pharmacology
chemical_list: D014528:Uricosuric Agents; D015237:Dinoprost; D015232:Dinoprostone; D011339:Probenecid