title: Developmental regulation of prostaglandin E2 synthase in porcine ductus arteriosus.
abstract: The synthesis of PGE(2), the major vasodilator prostanoid of the ductus arteriosus (DA), is catalyzed by PGE(2) synthases (PGES). The factors implicated in increased PGE(2) synthesis in the perinatal DA are not known. We studied the developmental changes of PGES along with that of cyclooxygenase (COX)-2 and cytosolic phospholipase A(2) (cPLA(2)) in the DA of fetal (75-90% gestation) and immediately postnatal newborn (NB) piglets. Levels of microsomal PGES (mPGES), COX-2, and PGE(2) in the DA of NB were approximately 7-fold higher than in fetus; activities of cytosolic PGES (cPGES) and cPLA(2) in DA of the fetus and NB did not differ. Because platelet-activating factor (PAF) could regulate COX-2 expression, the former was measured and found to be more abundant in the DA of the NB than of fetus. PAF elicited an increase in mPGES, COX-2, and PGE(2) in fetal DA to levels approaching those of the NB; cPGES, cPLA(2), and COX-1 were unaffected. In perinatal NB DA, PAF receptor antagonists BN-52021 and THG-315 reduced mPGES, COX-2, and PGE(2) levels and were associated with increased DA tone. It is concluded that PAF contributes in regulating DA tone by governing mPGES, COX-2, and ensuing PGE(2) levels in the perinate.
authors.affiliation: FRCP(C) Research Center, Sainte-Justine Hospital, 3175 Côte Ste-Catherine, Montréal, Quebec H3T 1C5, Canada. sylvain.chemtob@umontreal.ca
authors.forename: Asmàa
authors.initials: A
authors.lastname: Bouayad
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Fouron
authors.forename: Xin
authors.initials: X
authors.lastname: Hou
authors.forename: Martin
authors.initials: M
authors.lastname: Beauchamp
authors.forename: Christiane
authors.initials: C
authors.lastname: Quiniou
authors.forename: Daniel
authors.initials: D
authors.lastname: Abran
authors.forename: Krishna
authors.initials: K
authors.lastname: Peri
authors.forename: Ronald I
authors.initials: RI
authors.lastname: Clyman
authors.forename: Daya R
authors.initials: DR
authors.lastname: Varma
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chemtob
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051546:Cyclooxygenase 2; D003600:Cytosol / Q000201:enzymology; D015232:Dinoprostone / Q000378:metabolism*; D004373:Ductus Arteriosus / Q000196:embryology / Q000201:enzymology*; D066298:In Vitro Techniques; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013552:Swine
chemical_list: D007527:Isoenzymes; D010972:Platelet Activating Factor; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone