Developmental Changes in Prostaglandin E 2 Receptor Subtypes in Porcine Ductus Arteriosus Possible Contribution in Altered Responsiveness to Prostaglandin E 2

Background—Prostaglandin E2 (PGE2) is important in ductus arteriosus (DA) patency, but the types of functional PGE2 receptors (EP) in the developing DA are not known. We postulated that age-dependent alterations in EP and/or their subtypes may possibly contribute to the reduced responsiveness of the newborn DA to PGE2. Methods and Results—We determined PGE2 receptor subtypes by competition binding and immunoblot studies on the DA of fetal (≈75% and 90% gestation) and newborn (<45 minutes old) pigs. We studied the effects of EP receptor stimulation on cAMP signaling in vitro and on term newborn (<3 hours old) DA patency in vivo. Fetal pig DA expressed EP2, EP3, and EP4 receptors equivalently, but not EP1. In neonatal DA, EP1, EP3, and EP4 were undetectable, whereas EP2 density was similar in fetus and newborn. Prostaglandin-induced changes in cAMP mirrored binding data. 16,16-Dimethyl PGE2 and 11-deoxy PGE1 (EP2/EP3/EP4 agonist) produced more cAMP in fetus than newborn, but butaprost (selective EP2 agonist...