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Drug Metabolism and Disposition Fast Forward
First published on December 28, 2005; DOI: 10.1124/dmd.105.006932


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Received for publication August 22, 2005.
Revised December 12, 2005.
Accepted for publication December 14, 2005.

Tissue Distribution and Ontogeny of Organic Cation Transporters in Mice

Yazen Alnouti 1, Jay S Petrick 1, Curtis D Klaassen 1*

1 University of Kansas Medical Center

* Address correspondence to: E-mail: cklassee{at}kumc.edu

Abstract

Organic cation transporters (Octs) play an important role in transporting cationic xeno- and endobiotics across biological membranes. Little is known about Octs in mice, therefore the tissue distribution and developmental changes in the mRNA expression of Octs in mice were quantified. Oct1, Oct2, Oct3, Octn1, Octn2, and Octn3 mRNA expression was quantified in 14 tissues from male and female mice using the branched DNA signal amplification assay (bDNA). Oct1 mRNA expression was highest in kidney, followed by liver. Oct2 mRNA was almost exclusively expressed in kidney, with male mice having twice that in female mice. The higher expression of Oct2 in male mice is due to testosterone. Oct3 mRNA was most highly expressed in placenta, ovary, and uterus, but was expressed at low levels in most tissues. Octn1 and Octn2 mRNA expression was similar, with highest levels in kidney followed by small intestine. Octn3 mRNA was almost exclusively expressed in testes. The developmental expression of Oct1, Oct2, Octn1, and Octn2 mRNA in kidneys as well as Oct1 in livers was determined in young mice. Ontogenic expression data indicate that each of the Oct transporters approached adult expression levels by about three weeks of age. The gender difference in Oct mRNA expression did not become apparent until day 30 after birth. The differences in tissue distribution of the Octs may play an important role in drug disposition to various tissues. Furthermore, low expression of the Octs in young animals may affect the pharmacokinetic behavior of drugs compared to that in adults.


Key words: active transport, distribution, organic cation transport, transporters


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