RT Journal Article
SR Electronic
T1 Tissue Expression, Ontogeny, and Inducibility of Rat Organic Anion Transporting Polypeptide 4
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 551
OP 560
DO 10.1124/jpet.301.2.551
VO 301
IS 2
A1 Ning Li
A1 Dylan P. Hartley
A1 Nathan J. Cherrington
A1 Curtis D. Klaassen
YR 2002
UL http://jpet.aspetjournals.org/content/301/2/551.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics