Gender-specific and developmental influences on the expression of rat organic anion transporters.
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.
Buist
Susan C N
SC
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160-7417, USA.
Cherrington
Nathan J
NJ
Choudhuri
Supratim
S
Hartley
Dylan P
DP
Klaassen
Curtis D
CD
D000375:Aging / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D004247:DNA / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008099:Liver / Q000254:growth & development / Q000378:metabolism; D008297:Male; D015345:Oligonucleotide Probes; D027362:Organic Anion Transport Protein 1 / Q000096:biosynthesis*; D029362:Organic Anion Transporters, Sodium-Independent / Q000096:biosynthesis*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D014018:Tissue Distribution
D015345:Oligonucleotide Probes; D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; D012333:RNA, Messenger; C088800:Slc22a7 protein, rat; C114338:organic anion transport protein 3; D004247:DNA