Developmental regulation of prostaglandin E2 synthase in porcine ductus arteriosus.
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.
Bouayad
Asmàa
A
FRCP(C) Research Center, Sainte-Justine Hospital, 3175 Côte Ste-Catherine, Montréal, Quebec H3T 1C5, Canada. sylvain.chemtob@umontreal.ca
Fouron
Jean-Claude
JC
Hou
Xin
X
Beauchamp
Martin
M
Quiniou
Christiane
C
Abran
Daniel
D
Peri
Krishna
K
Clyman
Ronald I
RI
Varma
Daya R
DR
Chemtob
Sylvain
S
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
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