title: Prostaglandin G/H synthase-2 is a major contributor of brain prostaglandins in the newborn.
abstract: In order to understand the molecular basis of the elevated cerebral prostaglandin levels in the newborn, we compared the expression of the mRNAs and proteins of prostaglandin G/H synthases (PGHS), PGHS-1 and PGHS-2, in various regions of the brain and the microvasculature of newborn (1-2-day-old) and juvenile (4-7-week-old) pigs and also measured the relative contribution of PGHS-2 to cerebral prostaglandin synthesis both in vivo and in vitro by using a novel inhibitor of PGHS-2, NS-398. Ribonuclease protection assays using total RNA isolated from various regions of the porcine brain revealed that, unlike PGHS-1 mRNA, PGHS-2 mRNA was abundantly expressed in the cortex and the microvasculature of the newborn compared with those of the juvenile animal. PGHS-2 immunoreactive protein comprised the majority of total PGHS enzyme in neonatal cerebral microvasculature due to a 2-3-fold lower expression of immunoreactive PGHS-1 protein. Inhibition of PGHS-2 by NS-398 decreased the rate of prostaglandin synthesis by purified cerebral microvessels of the newborn by approximately 65% and of juvenile pigs by 30%. The decrease in brain tissue prostaglandin concentrations following intravenous administration of NS-398 was greater in newborn pigs (> or = 90%) than in the juvenile animals (< or = 30%). Furthermore, NS-398 substantially reduced the net in vivo cerebrovascular production of prostaglandins in newborn pigs. Taken together, these results indicate that PGHS-2 is the predominant form of prostaglandin G/H synthase in the newborn brain and cerebral microvasculature and the main contributor to the brain prostaglandin levels in the newborn animal.
authors.affiliation: Research Centre, Ste. Justine Hospital, Montreal, Canada.
authors.forename: K G
authors.initials: KG
authors.lastname: Peri
authors.forename: P
authors.initials: P
authors.lastname: Hardy
authors.forename: D Y
authors.initials: DY
authors.lastname: Li
authors.forename: D R
authors.initials: DR
authors.lastname: Varma
authors.forename: S
authors.initials: S
authors.lastname: Chemtob
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001921:Brain / Q000098:blood supply / Q000201:enzymology* / Q000254:growth & development; D002540:Cerebral Cortex / Q000201:enzymology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D017931:DNA Primers; D015342:DNA Probes; D006801:Humans; D007082:Ileum / Q000098:blood supply; D007527:Isoenzymes / Q000096:biosynthesis*; D051379:Mice; D008833:Microcirculation / Q000201:enzymology* / Q000254:growth & development; D008969:Molecular Sequence Data; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011453:Prostaglandins / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology; D013552:Swine
chemical_list: D016861:Cyclooxygenase Inhibitors; D017931:DNA Primers; D015342:DNA Probes; D007527:Isoenzymes; D009578:Nitrobenzenes; D011453:Prostaglandins; D012333:RNA, Messenger; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D011451:Prostaglandin-Endoperoxide Synthases