Characterization of PGE2 receptors in fetal and newborn lamb ductus arteriosus.
Although the role of PGE2 in maintaining ductus arteriosus (DA) patency is well established, the specific PGE2 receptor subtype(s) (EP) involved have not been clearly identified. We used late gestation fetal and neonatal lambs to study developmental regulation of EP receptors. In the fetal DA, radioligand binding and RT-PCR assays virtually failed to detect EP1 but detected EP2, EP3D, and EP4 receptors in equivalent proportions. In the newborn lamb, DA total density was one-third of that found in the fetus and only EP2 was detected. Stimulation of EP2 and EP4 increased cAMP formation and was associated with DA relaxation. Though stimulation of EP3 inhibited cAMP formation, it surprisingly relaxed the fetal DA both in vitro and in vivo. This EP3-induced relaxation was specifically diminished by the ATP-sensitive K(+) (K(ATP)) channel blocker glibenclamide. In conclusion, PGE2 dilates the late gestation fetal DA through pathways that involve either cAMP (EP2 and EP4) or K(ATP) channels (EP3). The loss of EP3 and EP4 receptors in the newborn DA is consistent with its decreased responsiveness to PGE2.
Bouayad
A
A
Departments of Cardiology, Pediatrics, and Physiology, Université de Montréal, Quebec H3T 1C5, Canada.
Kajino
H
H
Waleh
N
N
Fouron
J C
JC
Andelfinger
G
G
Varma
D R
DR
Skoll
A
A
Vazquez
A
A
Gobeil
F
F
Clyman
R I
RI
Chemtob
S
S
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001667:Binding, Competitive; D001713:Biphenyl Compounds / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004373:Ductus Arteriosus / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000737:chemistry / Q000378:metabolism; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000378:metabolism; D011247:Pregnancy; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D011869:Radioligand Assay; D018078:Receptors, Prostaglandin E / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012756:Sheep; D014316:Tritium; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014966:Xanthenes / Q000494:pharmacology; D044004:Xanthones
D000889:Anti-Arrhythmia Agents; D000897:Anti-Ulcer Agents; D001713:Biphenyl Compounds; D015221:Potassium Channels; D011448:Prostaglandin Antagonists; D011459:Prostaglandins E, Synthetic; D018078:Receptors, Prostaglandin E; D014966:Xanthenes; D044004:Xanthones; D014316:Tritium; C067522:GR 63799X; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; C022934:16,16-dimethylprostaglandin F2alpha; C032405:11-deoxy-16-phenoxy-17,18,19,20-tetranorprostaglandin E1; C046926:AH 23848; D000255:Adenosine Triphosphate; D015237:Dinoprost; D000527:Alprostadil; C048491:butaprost