| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston, SC, USA
* To whom correspondence should be addressed. E-mail: sweetd{at}musc.edu.
An uncharacterized murine cDNA clone was identified and, through sequence, phylogenetic, and functional analysis, determined to encode the newest member of the organic anion transporter family, organic anion transporter 5 (Oat5; Slc22a19). The Oat5 cDNA clone contained an insert 1,964 base pairs in length with a predicted open reading frame (from base pair 84 to base pair 1,739) coding for a peptide 551 amino acids long. Slc22a19 was localized to mouse chromosome 19 near the genes encoding Oat1 (Slc22a6) and Oat3 (Slc22a8). Northern blotting revealed Oat5 is highly expressed in the kidney of adult mice and rats. No sexual dimorphism in renal or hepatic expression of Oat5 was observed. Unlike Oat1-3, Oat5 expression was not detected in the choroid plexus of either mice or rats. Murine Oat5-expressing Xenopus oocytes supported increased accumulation of the mycotoxin Ochratoxin A, as compared to water-injected control oocytes. This uptake was significantly inhibited by probenecid, and the organic anions 2,4-dichlorophenoxyacetic acid, salicylate, and estrone sulfate, but not by para-aminohippurate or urate. Transport of Ochratoxin A by murine Oat5 was saturable, with an estimated Km of 2.0 ± 0.45 µM. Oat5-mediated transport was neither cis-inhibited nor trans-stimulated by the dicarboxylate glutarate. Uptake was also completely unaffected by shortcircuiting of the membrane potential. Thus, the motive forces behind Oat5 function, which provide insight to its membrane localization, need to be further resolved. These data demonstrate for the first time that this newly identified gene encodes a protein that functions as an organic anion transporter.
This article has been cited by other articles:
|
|
 |
|
  S.-Y. Ahn and S. K. Nigam Toward a Systems Level Understanding of Organic Anion and Other Multispecific Drug Transporters: A Remote Sensing and Signaling Hypothesis Mol. Pharmacol., September 1, 2009; 76(3): 481 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Wu, M. E. Baker, S. A. Eraly, K. T. Bush, and S. K. Nigam Analysis of a large cluster of SLC22 transporter genes, including novel USTs, reveals species-specific amplification of subsets of family members Physiol Genomics, July 9, 2009; 38(2): 116 - 124. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Duan and G. You Novobiocin Is a Potent Inhibitor for Human Organic Anion Transporters Drug Metab. Dispos., June 1, 2009; 37(6): 1203 - 1210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Li, P. Duan, and G. You Regulation of human organic anion transporter 1 by ANG II: involvement of protein kinase C{alpha} Am J Physiol Endocrinol Metab, February 1, 2009; 296(2): E378 - E383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Di Giusto, N. Anzai, H. Endou, and A. M. Torres Oat5 and NaDC1 Protein Abundance in Kidney and Urine After Renal Ischemic Reperfusion Injury J. Histochem. Cytochem., January 1, 2009; 57(1): 17 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. VanWert, C. Srimaroeng, and D. H. Sweet Organic Anion Transporter 3 (Oat3/Slc22a8) Interacts with Carboxyfluoroquinolones, and Deletion Increases Systemic Exposure to Ciprofloxacin Mol. Pharmacol., July 1, 2008; 74(1): 122 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Klaassen and H. Lu Xenobiotic Transporters: Ascribing Function from Gene Knockout and Mutation Studies Toxicol. Sci., February 1, 2008; 101(2): 186 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Kwon, S.-M. Hong, and K. Blouch Alteration in Renal Organic Anion Transporter 1 After Ischemia/Reperfusion in Cadaveric Renal Allografts J. Histochem. Cytochem., June 1, 2007; 55(6): 575 - 584. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Schneider, C. Sauvant, B. Betz, M. Otremba, D. Fischer, H. Holzinger, C. Wanner, J. Galle, and M. Gekle Downregulation of organic anion transporters OAT1 and OAT3 correlates with impaired secretion of para-aminohippurate after ischemic acute renal failure in rats Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1599 - F1605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hagos, D. Stein, B. Ugele, G. Burckhardt, and A. Bahn Human Renal Organic Anion Transporter 4 Operates as an Asymmetric Urate Transporter J. Am. Soc. Nephrol., February 1, 2007; 18(2): 430 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. W. Schnabolk, G. L. Youngblood, and D. H. Sweet Transport of estrone sulfate by the novel organic anion transporter Oat6 (Slc22a20) Am J Physiol Renal Physiol, August 1, 2006; 291(2): F314 - F321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sekine, H. Miyazaki, and H. Endou Molecular physiology of renal organic anion transporters Am J Physiol Renal Physiol, February 1, 2006; 290(2): F251 - F261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sauvant, H. Holzinger, and M. Gekle Prostaglandin E2 Inhibits Its Own Renal Transport by Downregulation of Organic Anion Transporters rOAT1 and rOAT3 J. Am. Soc. Nephrol., January 1, 2006; 17(1): 46 - 53. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
