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Research ArticleArticle

Tissue Distribution and Renal Developmental Changes in Rat Organic Cation Transporter mRNA levels

A. L. Slitt, N. J. Cherrington, D. P. Hartley, T. M. Leazer and C. D. Klaassen
Drug Metabolism and Disposition February 2002, 30 (2) 212-219; DOI: https://doi.org/10.1124/dmd.30.2.212
A. L. Slitt
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N. J. Cherrington
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D. P. Hartley
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T. M. Leazer
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C. D. Klaassen
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Abstract

Organic cation transporters (OCTs) are responsible for excretion of cationic substances into urine. Tissue OCT expression may be important for the disposition and excretion of xenobiotics. Therefore, OCT1, OCT2, OCT3, OCTN1, and OCTN2 mRNA levels were measured in adult rat tissues and rat kidney tissue at various stages of development from day 0 to 45. OCT1 mRNA expression was highest in kidney and spleen, moderate in skin, and low in the gastrointestinal tract, brain, lung, thymus, muscle, and prostate. OCT2 mRNA levels were highest in kidney, with low expression in other tissues, and with renal OCT2 levels being approximately 4 times higher in males than that in females. In gonadectomized males, OCT2 mRNA levels were attenuated to female levels, suggesting a role for testosterone in OCT2 expression. OCT3 was moderately expressed in kidney and was highest in blood vessel, skin, and thymus. OCTN1 was expressed in most of the tissues examined, with relatively higher expression in kidney and ileum and lower levels in thymus. Lastly, OCTN2 was expressed abundantly in kidney and ileum, moderately in large intestine, dorsal prostate, bladder, duodenum, and cerebellum, and minimally in thymus, spleen, and cerebral cortex. Renal OCT1, OCTN1, and OCTN2 mRNA levels increased gradually from postnatal day 0 through day 45 in both genders. Renal OCT2 levels remained the same in males and females through day 25 and then dramatically increased only in male kidney after day 30. In summary, OCT mRNA was detected primarily in kidney, and the high level of renal OCT expression may explain why the kidney is a target organ for xenobiotics with cationic properties.

Footnotes

  • ↵1 Present address: Department of Drug Metabolism, Merck Research Laboratories, Rahway, NJ 07065.

  • A.L.S., N.J.C., D.P.H, and T.M.L. were supported by National Institutes of Health Grant ES-09649.

  • Abbreviations used are::
    TEA
    tetraethylammonium
    OCT
    organic cation transporter
    bDNA
    branched DNA
    RLU
    relative light units
    OC
    organic cation
    • Received August 13, 2001.
    • Accepted November 9, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 30 (2)
Drug Metabolism and Disposition
Vol. 30, Issue 2
1 Feb 2002
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Research ArticleArticle

Tissue Distribution and Renal Developmental Changes in Rat Organic Cation Transporter mRNA levels

A. L. Slitt, N. J. Cherrington, D. P. Hartley, T. M. Leazer and C. D. Klaassen
Drug Metabolism and Disposition February 1, 2002, 30 (2) 212-219; DOI: https://doi.org/10.1124/dmd.30.2.212

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Research ArticleArticle

Tissue Distribution and Renal Developmental Changes in Rat Organic Cation Transporter mRNA levels

A. L. Slitt, N. J. Cherrington, D. P. Hartley, T. M. Leazer and C. D. Klaassen
Drug Metabolism and Disposition February 1, 2002, 30 (2) 212-219; DOI: https://doi.org/10.1124/dmd.30.2.212
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