PROSTAGLANDIN RECEPTOR
SPECIFICITY IN REGULATION OF FETAL AND NEONATAL DUCTUS ARTERIOSUS
Gao J1,
Naoko B 2 and Reese J2
1. Second
University Hospital, Huaxi Medical Center, Sichuan University, Chengdu,
China
2. Department of
Pediatrics, Kansas University Medical Center, Kansas City, Kansas
Objective: To define the mechanisms of
Prostaglandin (PG) signaling in Ductus arteriosus (DA) regulation.
Methods: On day17, 18, 19 (full term) and on
postpartum day 1, fetal and newborn mice DA and aortic segments were
cleanly dissected from surrounding tissues. Total RNA from 5-6 pups was
subject to oligo-dT primed reverse transcription. cDNAs were amplified by
gene-specific primers for PGD (DP), PGE2 (EP1-4), PGF2a
(FP), prostacyclin (IP), thromboxane A2 (TP) and for the
nuclear receptors PPARa, d and g.
Southern blot showed specific patterns of PG receptor upregulation at term.
The cell-specific localization of DA-specific PG receptors was determined
by in situ hybridization.
Results: Results showed the EP1, EP3, TP and FP
have maximal expression at the time of delivery. EP4 expression was
relatively constant and highly localized to the DA. Surprisingly, IP
expression was very low, although prostacyclin signals may be transduced by
PPAR upregulation in the term fetal DA.
Conclusions: DA patency in utero and postnatal DA
closure are influenced by the differential actions of specific PG
receptors. Selective agonists and antagonists of these receptors may
improve therapies for PDAs or protect the fetal DA during tocolysis for
preterm labor.