PT  - JOURNAL ARTICLE
AU  - Ogasawara, Ken
AU  - Terada, Tomohiro
AU  - Asaka, Jun-ichi
AU  - Katsura, Toshiya
AU  - Inui, Ken-ichi
TI  - Human Organic Anion Transporter 3 Gene Is Regulated Constitutively and Inducibly via a cAMP-Response Element
AID  - 10.1124/jpet.106.108233
DP  - 2006 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 317--322
VI  - 319
IP  - 1
4099  - http://jpet.aspetjournals.org/content/319/1/317.short
4100  - http://jpet.aspetjournals.org/content/319/1/317.full
SO  - J Pharmacol Exp Ther2006 Oct 01; 319
AB  - Human organic anion transporter (OAT) 3 (SLC22A8) is localized to the basolateral membranes of renal tubular epithelial cells and plays a critical role in the excretion of anionic compounds. We previously reported that interindividual variation in the OAT3 mRNA level corresponded to interindividual differences in the rate of renal excretion of cefazolin. However, there is little information available on the molecular mechanisms regulating the gene expression of OAT3. Therefore, in the present study, we examined the transcriptional regulation of human OAT3. A deletion analysis of the OAT3 promoter suggested that the region spanning -214 to -77 base pairs was essential for basal transcriptional activity. This region contained a perfectly conserved cAMP-response element (CRE), and a mutation here led to a reduction in promoter activity. Electrophoretic mobility shift assays showed that CRE-binding protein (CREB)-1 and activating transcription factor (ATF)-1 bound to CRE. The activity of the OAT3 promoter was increased through the phosphorylation of CREB-1 and ATF-1 by treatment with 8-bromo-cAMP. This paper reports the first characterization of the human OAT3 promoter and shows that CREB-1 and ATF-1 function as constitutive and inducible transcriptional regulators of the human OAT3 gene via CRE. The American Society for Pharmacology and Experimental Therapeutics