title: Prostaglandin uptake and catabolism by the choroid plexus during development in sheep.
abstract: We have previously reported that prostaglandin(PG) E2 levels in sheep cerebrospinal fluid (CSF) are high prenatally and abate rapidly after birth. This event may contribute to the establishment of continuous breathing. To explain this change, we have examined PG disposal mechanisms in the perinatal and adult (pregnant and non-pregnant animal) sheep brain by measuring the capacity of the isolated choroid plexus to concentrate [3H]PGF2alpha and [3H]PGE2. At 0.9 gestation, [3H]PGF2alpha uptake (expressed as the tissue-to-medium ratio, T/M) attained a steady-state by 15 min and was maintained thereafter (T/M at 60 min, 5.6 +/- 0.6; n = 16). Likewise, [3H]PGE2 was taken up by the tissue, but the actual accumulation was smaller (T/M at 60 min, 2.6 +/- 0.2; n = 8). Thin-layer radiochromatographic analysis of the tissue following incubation with [3H]PGF2alpha showed that 55 +/- 4% (n = 10) of radioactivity migrated as the 15-keto-13,14-dihydro metabolite. [3H]PGF2alpha uptake decreased upon treatment with probenecid (1 mM) (T/M, 2.5 +/- 0.2; n = 10) or after adding unlabelled PGF2alpha to the medium (1-60 microM) (T/M at 60 microM, 1.8 +/- 0.1; n = 13). The yield of labelled metabolite was also lower when using excess PGF2alpha (14% of control at 60 microM; n = 13), while it was not affected by probenecid. Uptake of both PGs did not change through development, from 0.7 gestation to day 18 postnatal, and attained higher values in the pregnant adult. Conversely, PGF2alpha catabolism decreased postnatally 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 process, however, can account for the birth-related change in CSF PGE2.
authors.affiliation: Division of Neurosciences, The Hospital for Sick Children, Toronto, Ont., Canada.
authors.forename: N
authors.initials: N
authors.lastname: Krunic
authors.forename: S L
authors.initials: SL
authors.lastname: Adamson
authors.forename: I
authors.initials: I
authors.lastname: Bishai
authors.forename: F
authors.initials: F
authors.lastname: Coceani
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport / Q000187:drug effects; D002831:Choroid Plexus / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005314:Embryonic and Fetal Development; D005260:Female; D005865:Gestational Age; D018496:Hyperoxia; D007700:Kinetics; D011247:Pregnancy; D011339:Probenecid / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D012016:Reference Values; D012756:Sheep; D013395:Sucrose / Q000378:metabolism
chemical_list: D011453:Prostaglandins; D013395:Sucrose; D015237:Dinoprost; D015232:Dinoprostone; D011339:Probenecid