Abstract
Understanding the role of transporters in placental handling of xenobiotics across the maternal-fetal interface is essential to evaluate the pharmacological and toxicological potential of therapeutic agents, drugs of abuse, and other xenobiotics to which the mother is exposed during pregnancy. Therefore, the purpose of this study was to assess mRNA levels of various transporters in placenta and to compare these to levels in maternal liver and kidney, predominant organs of excretion, to determine which transporters are likely to have a role in xenobiotic transfer within the placenta. During late stage pregnancy, relative amounts of mRNA levels of 40 genes representing 11 families/group of transporters were assessed in placenta with respect to relative maternal liver and kidney mRNA levels. Members of the following transporter families were assessed: three multidrug resistance (Mdr), six multidrug resistance-associated protein (Mrp), eight organic anion-transporting polypeptide (Oatp), three organic anion transporters (Oat), five organic cation transporters (Oct), two bile acid transporters (Na+/taurocholate-cotransporting polypeptide and bile salt export protein), four metal (ZnT1, divalent metal transporter 1, Menkes and Wilsons), a prostaglandin, two peptide, two sterolin, and four nucleoside transporters. Of the 40 genes evaluated, 16 [Mdr1a and 1b, Mrp1 and 5, Oct3 and Octn1, Oatp3 and 12, four metal, a prostaglandin, AbcG8, equilibrative nucleoside transporter 1 (ENT1), and ENT2] were expressed in placenta at concentrations similar to or higher than in maternal liver and kidney. The abundance of these mRNA transcripts in placenta suggests a role for these transporters in placental transport of xenobiotics and supports their role in the transport of endogenous substances.
Footnotes
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Research supported by National Institute of Environmental Health Sciences Grants ES-03192, ES-09716, and ES-09649 and training Grant ES-07079.
- Abbreviations used are::
- gd
- gestation day
- bDNA
- branched DNA
- Ntcp
- Na+/taurocholate-cotransporting polypeptide
- Bsep
- bile salt export protein
- Oatp
- organic anion-transporting polypeptide
- Oat-K
- organic anion transporter K
- PGT
- prostaglandin transporter
- PEPT
- peptide transporter
- ZnT-1
- zinc transporter 1
- ATP7A
- Menkes transporter
- ATP7B
- Wilson's transporter
- Cnt
- concentrative nucleoside transporter
- Ent
- equilibrative nucleoside transporter
- RLU
- relative light units
- Mdr
- multiple drug resistance
- Oct
- organic cation transporter
- DMT1
- divalent metal transporter 1
- P-gp
- P-glycoproteins
- Mrp
- multidrug resistance-associated proteins
- AbcG5 and AbcG8
- sterolin transporters 1 and 2
- Received August 23, 2002.
- Accepted October 21, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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