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Vol. 31, Issue 2, 153-167, February 2003
Department of Pharmacology, Toxicology and Therapeutics, University
of Kansas Medical Center, Kansas City, Kansas
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.
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