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Vol. 301, Issue 1, 145-151, April 2002
Department of Pharmacology, Toxicology, and Therapeutics,
University of Kansas Medical Center, Kansas City, Kansas
Rat organic anion transporter 1 (Oat1), Oat2, and Oat3, members
of the organic anion transporter family, transport some organic anions
across cellular membranes. Previously, highest Oat1 and Oat3 mRNA
expression was reported in kidney and Oat2 in liver. However, gender
and developmental differences in Oat expression remain unknown. This
study describes gender- and age-specific patterns of rat organic anion
transporter expression in various tissues. Oat mRNA expression was
evaluated in adult male and female Sprague-Dawley rat tissues, and
developmental expression was also determined in kidneys of
Sprague-Dawley rats ranging in age from days 0 through 45. Expression
was quantified using branched-DNA signal amplification. Oat1 mRNA
expression was primarily observed in kidney. Surprisingly, Oat2 mRNA
expression was also highest in kidney rather than in liver. Moreover,
considerably higher Oat2 levels were seen in female kidney as compared
with male. Finally, Oat3 mRNA expression was highest in kidney of both
genders, whereas a male-predominant pattern was observed in liver. At
birth, all kidney Oat mRNA levels were low. Renal Oat1 expression
gradually increased throughout development, approaching adult levels at 30 days of age, where at days 40 and 45 Oat1 levels were greater in
males than females. Oat2 expression in kidney was minimal through day
30 but increased dramatically at day 35 in females only. Lastly, Oat3
mRNA expression in kidney matured earliest, rapidly increasing from
birth through day 10. These data indicate that Oat mRNA expression is
primarily localized to the kidney, and observed expression patterns may
explain some previously recognized age- and gender-dependent toxicities
associated with chemical exposure.
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