Temporal expression profiles of organic anion transport proteins in placenta and fetal liver of the rat
Open Access
- 1 December 2004
- journal article
- Published by American Physiological Society in American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Vol. 287 (6), R1505-R1516
- https://doi.org/10.1152/ajpregu.00279.2003
Abstract
Physiological cholestasis linked to immature hepatobiliary transport systems for organic anions occurs in rat and human neonates. In utero, the placenta facilitates vectorial transfer of certain fetal-derived solutes to the maternal circulation for elimination. We compared the ontogenesis of organic anion transporters in the placenta and the fetal liver of the rat to assess their relative abundance throughout gestation and to determine whether the placenta compensates for the late maturation of transporters in the developing liver. The mRNA of members of the organic anion transporting polypeptide (Oatp) superfamily, the multidrug resistance protein (Mrp) family, one organic anion transporter (OAT), and the bile acid carriers Na+-taurocholate cotransporting polypeptide (Ntcp) and bile salt export pump (Bsep) was quantified by real-time PCR. The most abundant placental transporters were Oatp4a1, whose mRNA increased 10-fold during gestation, and Mrp1. Mrp1 immunolocalized predominantly to epithelial cells of the endoplacental yolk sac, suggesting an excretory role that sequesters fetal-derived solutes in the yolk sac cavity, and faintly to the basal syncytiotrophoblast surface. The mRNA levels of Oatp2b1, Mrp3, and Bsep in the placenta exceeded those in the fetal liver until day 20 of gestation, suggesting that the fetus relies on placental clearance of substrates when expression in the developing liver is low. Mrp3 immunolocalized to the epithelium of the endoplacental yolk sac and less abundantly in the labyrinth zone and endothelium of the maternal arteries. The placental expression of Oatp1a1, Oatp1a4, Oatp1a5, Oatp1b2, Oat, Ntcp, Mrp2, and Mrp6 was low.Keywords
This publication has 61 references indexed in Scilit:
- Differential expression of bile salt and organic anion transporters in developing rat liverJournal of Hepatology, 2004
- Cloning and characterization of the rat multidrug resistance-associated protein 1AAPS PharmSci, 2002
- Postnatal Expression and Induction by Pregnenolone-16α-Carbonitrile of the Organic Anion-Transporting Polypeptide 2 in Rat LiverDrug Metabolism and Disposition, 2002
- Organ Distribution of Multidrug Resistance Proteins 1, 2, and 3 (Mrp1, 2, and 3) mRNA and Hepatic Induction of Mrp3 by Constitutive Androstane Receptor Activators in RatsThe Journal of pharmacology and experimental therapeutics, 2002
- Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assaysJournal of Molecular Endocrinology, 2000
- Molecular Identification of a Rat Novel Organic Anion Transporter moat1, Which Transports Prostaglandin D2, Leukotriene C4, and TaurocholateBiochemical and Biophysical Research Communications, 2000
- Multidrug resistance protein MRP1 protects against the toxicity of the major lipid peroxidation product 4-hydroxynonenalBiochemical Journal, 2000
- Expression of Multidrug Resistance Protein/GS-X Pump and γ-Glutamylcysteine Synthetase Genes Is Regulated by Oxidative StressJournal of Biological Chemistry, 1998
- Differential Ontogenic Regulation of Basolateral and Canalicular Bile Acid Transport Proteins in Rat LiverPublished by Elsevier BV ,1995
- ABC Transporters: From Microorganisms to ManAnnual Review of Cell Biology, 1992