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Vol. 301, Issue 2, 551-560, May 2002
Department of Pharmacology, Toxicology, and Therapeutics,
University of Kansas Medical Center, Kansas City, Kansas
To date, organic anion transporting polypeptide 4 (Oatp4; Slc21a10) is
known as a liver-specific and sodium-independent transporter that
mediates transport of a variety of compounds. The purpose of this study
was to determine whether Oatp4 mRNA expression is specific to the liver
compared with Oatp1, 2, 3, or 5. In addition, the effect of gender and
age was determined by assessing the expression of Oatp4 mRNA during the
postnatal development of rats. Furthermore, to determine whether Oatp4
gene expression is coordinately modulated by drug-metabolizing enzyme
inducers, male rats were administered chemicals known to induce the
expression of drug-metabolizing enzymes through six mechanisms: the
aryl hydrocarbon receptor, constitutive androstane receptor,
pregnane X receptor, peroxisome proliferator-activated receptor,
electrophile response element, or CYP2E1 inducers. The levels of Oatp1,
2, 3, 4, and 5 mRNA were measured using the branched DNA signal
amplification technique. The tissue distribution of Oatp4 was almost
exclusively expressed in liver in contrast to Oatp1, 2, 3, and 5. The
hepatic expression of Oatp4 was low in newborn rats and increased
gradually to the adult level with no significant difference between
genders. The expression of Oatp4 was not consistently induced by any of
the six groups of enzyme inducers. These findings continue to suggest that Oatp4 is expressed specifically in the liver. The preference of
Oatp4 for endogenous compounds coupled with its refractory response to
known drug-metabolizing enzyme inducers suggests that Oatp4 may be
largely responsible for the homeostasis of endogenous rather than
exogenous chemicals, including pharmaceuticals.
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