organic anion transport protein 1

Summary

Summary: A polyspecific transporter for organic cations found primarily in the kidney. It mediates the coupled exchange of alpha-ketoglutarate with organic ions such as P-AMINOHIPPURIC ACID.

Top Publications

  1. Saji T, Kikuchi R, Kusuhara H, Kim I, Gonzalez F, Sugiyama Y. Transcriptional regulation of human and mouse organic anion transporter 1 by hepatocyte nuclear factor 1 alpha/beta. J Pharmacol Exp Ther. 2008;324:784-90 pubmed
    ..These results provide convincing evidence for the involvement of HNF1alpha/beta in the constitutive expression of human and mouse OAT1 in the kidney. ..
  2. Ogasawara K, Terada T, Asaka J, Katsura T, Inui K. Hepatocyte nuclear factor-4{alpha} regulates the human organic anion transporter 1 gene in the kidney. Am J Physiol Renal Physiol. 2007;292:F1819-26 pubmed
    ..This paper reports the first characterization of the human OAT1 promoter and the first gene in the kidney whose promoter activity is regulated by HNF-4alpha. ..
  3. Kojima R, Sekine T, Kawachi M, Cha S, Suzuki Y, Endou H. Immunolocalization of multispecific organic anion transporters, OAT1, OAT2, and OAT3, in rat kidney. J Am Soc Nephrol. 2002;13:848-57 pubmed
    ..These results on the distribution of each OAT isoform will facilitate the understanding of the role of OATs in the renal processing of organic anions. ..
  4. Cerrutti J, Brandoni A, Quaglia N, Torres A. Sex differences in p-aminohippuric acid transport in rat kidney: role of membrane fluidity and expression of OAT1. Mol Cell Biochem. 2002;233:175-9 pubmed
  5. Di Giusto G, Anzai N, Ruiz M, Endou H, Torres A. Expression and function of Oat1 and Oat3 in rat kidney exposed to mercuric chloride. Arch Toxicol. 2009;83:887-97 pubmed publisher
    ..The pharmacological modulation of the expression and/or the function of Oat1 and Oat3 might be an effective therapeutic strategy for reducing the nephrotoxicity of mercury...
  6. Cihlar T, Laflamme G, Fisher R, Carey A, Vela J, Mackman R, et al. Novel nucleotide human immunodeficiency virus reverse transcriptase inhibitor GS-9148 with a low nephrotoxic potential: characterization of renal transport and accumulation. Antimicrob Agents Chemother. 2009;53:150-6 pubmed publisher
    ..Compared to acyclic nucleotide analogs, GS-9148 was also found to have lower net active tubular secretion in dogs. Collectively, these results suggest that GS-9148 exhibits a low potential for renal accumulation and nephrotoxicity. ..
  7. Kiser J, Aquilante C, Anderson P, King T, Carten M, Fletcher C. Clinical and genetic determinants of intracellular tenofovir diphosphate concentrations in HIV-infected patients. J Acquir Immune Defic Syndr. 2008;47:298-303 pubmed
    ..04). This study provides direction for future investigations to elucidate the contribution of clinical characteristics and drug transporter genotype to TFV-DP safety and efficacy. ..
  8. Truong D, Kaler G, Khandelwal A, Swaan P, Nigam S. Multi-level analysis of organic anion transporters 1, 3, and 6 reveals major differences in structural determinants of antiviral discrimination. J Biol Chem. 2008;283:8654-63 pubmed publisher
  9. Schneider R, Sauvant C, Betz B, Otremba M, Fischer D, Holzinger H, et al. 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. 2007;292:F1599-605 pubmed
    ..As a result, this may have substantial impact on excretion kinetics and half-life of organic anions. As a consequence, the biological effects of a variety of organic anions may be affected after iARF. ..

More Information

Publications97

  1. Lash L, Putt D, Cai H. Membrane transport function in primary cultures of human proximal tubular cells. Toxicology. 2006;228:200-18 pubmed
  2. Servais A, Lechat P, Zahr N, Urien S, Aymard G, Jaudon M, et al. Tubular transporters and clearance of adefovir. Eur J Pharmacol. 2006;540:168-74 pubmed
    ..Additional pharmacological inhibition of transporters decreased renal clearance, which may reflect inhibition of compensating transport mechanisms activated when MRP2 is lacking. ..
  3. Eraly S, Vallon V, Vaughn D, Gangoiti J, Richter K, Nagle M, et al. Decreased renal organic anion secretion and plasma accumulation of endogenous organic anions in OAT1 knock-out mice. J Biol Chem. 2006;281:5072-83 pubmed
    ..We have also demonstrated in xenopus oocytes that some of these compounds interact with OAT1 in vitro. Thus, these latter compounds might represent physiological substrates of OAT1. ..
  4. Kohler J, Hosseini S, Green E, Abuin A, Ludaway T, Russ R, et al. Tenofovir renal proximal tubular toxicity is regulated by OAT1 and MRP4 transporters. Lab Invest. 2011;91:852-8 pubmed publisher
    ..Disruption of OAT1 activity prevents tenofovir toxicity but loss of MRP4 can lead to increased renal proximal tubular toxicity. These data help to explain mechanisms of human TDF renal toxicity. ..
  5. Ljubojevic M, Herak Kramberger C, Hagos Y, Bahn A, Endou H, Burckhardt G, et al. Rat renal cortical OAT1 and OAT3 exhibit gender differences determined by both androgen stimulation and estrogen inhibition. Am J Physiol Renal Physiol. 2004;287:F124-38 pubmed
  6. Deguchi T, Kusuhara H, Takadate A, Endou H, Otagiri M, Sugiyama Y. Characterization of uremic toxin transport by organic anion transporters in the kidney. Kidney Int. 2004;65:162-74 pubmed
    ..Both OAT1 and OAT3 contribute almost equally to the renal uptake of IS. OAT3 mainly accounts for CMPF uptake by the kidney, while OAT1 mainly accounts for IA and HA uptake. ..
  7. Miller D. Nucleoside phosphonate interactions with multiple organic anion transporters in renal proximal tubule. J Pharmacol Exp Ther. 2001;299:567-74 pubmed
    ..Comparison of the inhibitory potencies of the nucleoside phosphonates with other substrates and inhibitors showed them to be moderate inhibitors of OAT1- and Mrp2-mediated transport. ..
  8. Jung K, Takeda M, Kim D, Tojo A, Narikawa S, Yoo B, et al. Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001;69:2123-35 pubmed
    ..These pharmacological characteristics of hOAT1 and hOAT3 may be significantly related with the events in the development of OTA-induced nephrotoxicity in the human kidney. ..
  9. Sweet D, Wolff N, Pritchard J. Expression cloning and characterization of ROAT1. The basolateral organic anion transporter in rat kidney. J Biol Chem. 1997;272:30088-95 pubmed
    ..Each of these properties is identical to those previously described for the basolateral alpha-ketoglutarate/PAH exchanger in isolated membrane vesicles or intact renal tubules. ..
  10. Bakhiya N, Batke M, Laake J, Monien B, Frank H, Seidel A, et al. Directing role of organic anion transporters in the excretion of mercapturic acids of alkylated polycyclic aromatic hydrocarbons. Drug Metab Dispos. 2007;35:1824-31 pubmed
  11. Kelly K, Kluve Beckerman B, Zhang J, Dominguez J. Intravenous cell therapy for acute renal failure with serum amyloid A protein-reprogrammed cells. Am J Physiol Renal Physiol. 2010;299:F453-64 pubmed publisher
    ..We conclude that infusions of SAA-positive cells promote renal recovery after acute renal failure and offer a potentially powerful and novel therapy of renal failure. ..
  12. Fujita T, Brown C, Carlson E, Taylor T, De La Cruz M, Johns S, et al. Functional analysis of polymorphisms in the organic anion transporter, SLC22A6 (OAT1). Pharmacogenet Genomics. 2005;15:201-9 pubmed
  13. Lam J, Shugarts S, Okochi H, Benet L. Elucidating the effect of final-day dosing of rifampin in induction studies on hepatic drug disposition and metabolism. J Pharmacol Exp Ther. 2006;319:864-70 pubmed
    ..To observe full inductive effects, test drugs should be administered 1 day after final dosing of RIF to minimize potential organic anion transporting polypeptide inhibition effects. ..
  14. Favretto G, Souza L, Gregório P, Cunha R, Maciel R, Sassaki G, et al. Role of Organic Anion Transporters in the Uptake of Protein-Bound Uremic Toxins by Human Endothelial Cells and Monocyte Chemoattractant Protein-1 Expression. J Vasc Res. 2017;54:170-179 pubmed publisher
    ..MCP-1 expression increased after toxins treatment but decreased after Pb treatment. PCS and IS uptake were mediated by OATs, and OAT blockage could serve as a therapeutic strategy to inhibit MCP-1 expression. ..
  15. Nishihara K, Masuda S, Ji L, Katsura T, Inui K. Pharmacokinetic significance of luminal multidrug and toxin extrusion 1 in chronic renal failure rats. Biochem Pharmacol. 2007;73:1482-90 pubmed
  16. Bhatnagar V, Xu G, Hamilton B, Truong D, Eraly S, Wu W, et al. Analyses of 5' regulatory region polymorphisms in human SLC22A6 (OAT1) and SLC22A8 (OAT3). J Hum Genet. 2006;51:575-80 pubmed
    ..The clustering of OAT genes in the genome raises the possibility that nucleotide polymorphisms in SLC22A6 could also effect SLC22A8 expression, and vice versa. ..
  17. Zalups R, Ahmad S. Handling of the homocysteine S-conjugate of methylmercury by renal epithelial cells: role of organic anion transporter 1 and amino acid transporters. J Pharmacol Exp Ther. 2005;315:896-904 pubmed
    ..Collectively, the present data indicate that CH(3)Hg-Hcy is a transportable substrate of OAT1 and amino acid transporters and, thus, is probably a transportable mercuric species taken up in vivo by proximal tubular epithelial cells. ..
  18. Hong M, Tanaka K, Pan Z, Ma J, You G. Determination of the external loops and the cellular orientation of the N- and the C-termini of the human organic anion transporter hOAT1. Biochem J. 2007;401:515-20 pubmed
    ..These studies provided the first experimental evidence on the extracellular loops and the cellular orientation of the N- and the C-termini of hOAT1. ..
  19. Kaler G, Truong D, Khandelwal A, Nagle M, Eraly S, Swaan P, et al. Structural variation governs substrate specificity for organic anion transporter (OAT) homologs. Potential remote sensing by OAT family members. J Biol Chem. 2007;282:23841-53 pubmed
    ..g. olfactory mucosa). We also discuss how these data suggest a possible mechanism for remote sensing between OATs in different tissue compartments (e.g. kidney, olfactory mucosa) via organic anions. ..
  20. Spitzenberger F, Graessler J, Schroeder H. Molecular and functional characterization of galectin 9 mRNA isoforms in porcine and human cells and tissues. Biochimie. 2001;83:851-62 pubmed
    ..The data of the present study sustain the idea of the involvement of galectin 9 in immune/inflammation processes and in potential-sensitive uric acid translocation. ..
  21. Chen J, Terada T, Ogasawara K, Katsura T, Inui K. Adaptive responses of renal organic anion transporter 3 (OAT3) during cholestasis. Am J Physiol Renal Physiol. 2008;295:F247-52 pubmed publisher
    ..In conclusion, the present study clearly demonstrated that OAT3 is responsible for renal secretion of bile acids during cholestasis and that the pharmacokinetic profile of OAT3 substrates may be affected by cholestasis. ..
  22. Zalups R, Ahmad S. Transport of N-acetylcysteine s-conjugates of methylmercury in Madin-Darby canine kidney cells stably transfected with human isoform of organic anion transporter 1. J Pharmacol Exp Ther. 2005;314:1158-68 pubmed
  23. Kobayashi Y, Hirokawa N, Ohshiro N, Sekine T, Sasaki T, Tokuyama S, et al. Differential gene expression of organic anion transporters in male and female rats. Biochem Biophys Res Commun. 2002;290:482-7 pubmed
    ..Our results provide information on the differential gene expression of OAT isoforms with sex hormone dependency. ..
  24. Dickman K, Sweet D, Bonala R, Ray T, Wu A. Physiological and molecular characterization of aristolochic acid transport by the kidney. J Pharmacol Exp Ther. 2011;338:588-97 pubmed publisher
    ..Taken together, these findings indicate that OAT family members mediate high-affinity transport of AA-I and may be involved in the site-selective toxicity and renal elimination of this nephrotoxin. ..
  25. Xu G, Bhatnagar V, Wen G, Hamilton B, Eraly S, Nigam S. Analyses of coding region polymorphisms in apical and basolateral human organic anion transporter (OAT) genes [OAT1 (NKT), OAT2, OAT3, OAT4, URAT (RST)]. Kidney Int. 2005;68:1491-9 pubmed
    ..Certain OAT family members appear to be under greater evolutionary selection pressure. ..
  26. Hocherl K, Schmidt C, Bucher M. COX-2 inhibition attenuates endotoxin-induced downregulation of organic anion transporters in the rat renal cortex. Kidney Int. 2009;75:373-80 pubmed publisher
    ..Our findings show that COX-2 derived prostanoids downregulate OATs during lipopolysaccharide-induced acute renal injury. ..
  27. Rost D, Herrmann T, Sauer P, Schmidts H, Stieger B, Meier P, et al. Regulation of rat organic anion transporters in bile salt-induced cholestatic hepatitis: effect of ursodeoxycholate. Hepatology. 2003;38:187-95 pubmed
    ..In conclusion, we show that CA feeding may cause cholestasis associated with a posttranscriptional down-regulation of Oatp4. UDCA may prevent impairment of hepatic function by restoring hepatic transporter expression. ..
  28. Srinivas N. Is there a place for drug combination strategies using clinical pharmacology attributes?--review of current trends in research. Curr Clin Pharmacol. 2009;4:220-8 pubmed
    ..In summary, based on the collated information, a pragmatic approach would render feasibility for a balanced therapy management using combined clinical pharmacology attributes of drugs. ..
  29. Sakurai Y, Motohashi H, Ueo H, Masuda S, Saito H, Okuda M, et al. Expression levels of renal organic anion transporters (OATs) and their correlation with anionic drug excretion in patients with renal diseases. Pharm Res. 2004;21:61-7 pubmed
    ..These results suggest that hOAT3 plays an important role for anionic drug secretion in patients with renal diseases and that the expression levels of drug transporters may be related to the alteration of renal drug secretion. ..
  30. Sugawara M, Mochizuki T, Takekuma Y, Miyazaki K. Structure-affinity relationship in the interactions of human organic anion transporter 1 with caffeine, theophylline, theobromine and their metabolites. Biochim Biophys Acta. 2005;1714:85-92 pubmed
    ..The main determinant of the affinity of xanthine-related compounds is the position of the methyl group. On the other hand, lipophilicity is the main determinant of the affinity of uric acid-related compounds. ..
  31. Bahn A, Ebbinghaus C, Ebbinghaus D, Ponimaskin E, Fuzesi L, Burckhardt G, et al. Expression studies and functional characterization of renal human organic anion transporter 1 isoforms. Drug Metab Dispos. 2004;32:424-30 pubmed
  32. Hong M, Zhou F, Lee K, You G. The putative transmembrane segment 7 of human organic anion transporter hOAT1 dictates transporter substrate binding and stability. J Pharmacol Exp Ther. 2007;320:1209-15 pubmed
    ..Therefore, Trp-346 and Thr-349 are critically involved in the stability of the transporter. ..
  33. Ng K, Lim B, Wong K. Sulfate conjugating and transport functions of MDCK distal tubular cells. Kidney Int. 2003;63:976-86 pubmed
    ..Based on the action of specific inhibitors and modulators of MRP2 and OATP1, it was concluded that MRP2-like and OATP1-like transporters are possibly responsible for the transport of sulfated conjugates. ..
  34. Ianculescu A, Giacomini K, Scanlan T. Identification and characterization of 3-iodothyronamine intracellular transport. Endocrinology. 2009;150:1991-9 pubmed publisher
    ..This type of transporter small interfering RNA screening approach can be used in general to identify the constellation of transporters that participate in the intracellular disposition of compounds. ..
  35. Wang L, Pan X, Sweet D. The anthraquinone drug rhein potently interferes with organic anion transporter-mediated renal elimination. Biochem Pharmacol. 2013;86:991-6 pubmed publisher
    ..e., pharmacokinetics and pharmacodynamics) of co-administered hOAT1 and/or hOAT3 drug substrates. ..
  36. Wong C, Akiyama Y, Abe T, Lippiat J, Orfila C, Williamson G. Carrier-mediated transport of quercetin conjugates: involvement of organic anion transporters and organic anion transporting polypeptides. Biochem Pharmacol. 2012;84:564-70 pubmed publisher
    ..siRNA knockdown of OATP4C1 expression in HepG2 cells reduced uptake of quercetin-3'-O-sulfate by ?40%. This study highlights a role for OATs and OATPs in the cellular uptake of biologically active flavonoid conjugates. ..
  37. Elsby R, Fox L, Stresser D, Layton M, Butters C, Sharma P, et al. In vitro risk assessment of AZD9056 perpetrating a transporter-mediated drug-drug interaction with methotrexate. Eur J Pharm Sci. 2011;43:41-9 pubmed publisher
  38. Bleasby K, Hall L, Perry J, Mohrenweiser H, Pritchard J. Functional consequences of single nucleotide polymorphisms in the human organic anion transporter hOAT1 (SLC22A6). J Pharmacol Exp Ther. 2005;314:923-31 pubmed
  39. Mizuno N, Takahashi T, Iwase Y, Kusuhara H, Niwa T, Sugiyama Y. Human organic anion transporters 1 (hOAT1/SLC22A6) and 3 (hOAT3/SLC22A8) transport edaravone (MCI-186; 3-methyl-1-phenyl-2-pyrazolin-5-one) and its sulfate conjugate. Drug Metab Dispos. 2007;35:1429-34 pubmed
    ..In conclusion, our results suggest that both hOAT1 and hOAT3 are responsible for the basolateral uptake of edaravone sulfate in the kidney. ..
  40. Kim G, Na K, Kim S, Joo K, Oh Y, Chae S, et al. Up-regulation of organic anion transporter 1 protein is induced by chronic furosemide or hydrochlorothiazide infusion in rat kidney. Nephrol Dial Transplant. 2003;18:1505-11 pubmed
    ..34). Chronic furosemide or hydrochlorothiazide infusion caused increases in OAT1 protein abundance in rat kidney. These results suggest that OAT1 may be up-regulated in vivo by substrate stimulation at the protein level. ..
  41. Umehara K, Shirai N, Iwatsubo T, Noguchi K, Usui T, Kamimura H. Identification of human metabolites of (-)-N-{2-[(R)-3-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)piperidino]ethyl}-4-fluorobenzamide (YM758), a novel If channel inhibitor, and investigation of the transporter-mediated renal and hepatic. Drug Metab Dispos. 2009;37:1646-57 pubmed publisher
    ..This kind of study was useful in investigating the relationship between the urinary/hepatic elimination and the transport activity for metabolites. ..
  42. Shibayama Y, Ushinohama K, Ikeda R, Yoshikawa Y, Motoya T, Takeda Y, et al. Effect of methotrexate treatment on expression levels of multidrug resistance protein 2, breast cancer resistance protein and organic anion transporters Oat1, Oat2 and Oat3 in rats. Cancer Sci. 2006;97:1260-6 pubmed
    ..In conclusion, these data indicate that MTX treatment down-regulates expression levels of Mrp2, Oat1 and Oat3, and its effects are recovered by leucovorin...
  43. Aslamkhan A, Thompson D, Perry J, Bleasby K, Wolff N, Barros S, et al. The flounder organic anion transporter fOat has sequence, function, and substrate specificity similarity to both mammalian Oat1 and Oat3. Am J Physiol Regul Integr Comp Physiol. 2006;291:R1773-80 pubmed
    ..Furthermore, phylogenetic analyses argue that the teleost Oat1/3-like genes diverged from a common ancestral gene in advance of the divergence of the mammalian OAT1/Oat1, OAT3/Oat3, and, possibly, Oat6 genes. ..
  44. Bakhiya N, Stephani M, Bahn A, Ugele B, Seidel A, Burckhardt G, et al. Uptake of chemically reactive, DNA-damaging sulfuric acid esters into renal cells by human organic anion transporters. J Am Soc Nephrol. 2006;17:1414-21 pubmed
    ..This study indicates that OAT can mediate the basolateral uptake of reactive sulfuric acid esters into proximal tubule cells and thereby participate in kidney cell damage by these compounds. ..
  45. Takekuma Y, Kakiuchi H, Yamazaki K, Miyauchi S, Kikukawa T, Kamo N, et al. Difference between pharmacokinetics of mycophenolic acid (MPA) in rats and that in humans is caused by different affinities of MRP2 to a glucuronized form. J Pharm Pharm Sci. 2007;10:71-85 pubmed
    ..The affinity of rMRP2 to MPAG was about 3.6 times as high as that of hMRP2. Therefore, the difference of affinity between hMRP2 and rMrp2 is a possible mechanism of the difference of excretion ratio of MPAG between rats and human. ..
  46. Hasegawa M, Kusuhara H, Endou H, Sugiyama Y. Contribution of organic anion transporters to the renal uptake of anionic compounds and nucleoside derivatives in rat. J Pharmacol Exp Ther. 2003;305:1087-97 pubmed
    ..These results suggest that the renal uptake of 2,4-D is mainly accounted for by rOat1 and the uptake of PCG and DHEAS by rOat3, and rOat3 is partly involved in the renal uptake of temocaprilat and estrone sulfate. ..
  47. Wang L, Sweet D. Competitive inhibition of human organic anion transporters 1 (SLC22A6), 3 (SLC22A8) and 4 (SLC22A11) by major components of the medicinal herb Salvia miltiorrhiza (Danshen). Drug Metab Pharmacokinet. 2013;28:220-8 pubmed
    ..Thus, herb-drug interactions may occur in vivo in situations of co-administration of Danshen and clinical therapeutics known to be hOAT1/hOAT3 substrates. ..
  48. Hong M, Li S, Zhou F, Thomas P, You G. Putative transmembrane domain 12 of the human organic anion transporter hOAT1 determines transporter stability and maturation efficiency. J Pharmacol Exp Ther. 2010;332:650-8 pubmed publisher
    ..Our results are the first to highlight the central role of TM 12 in maintaining the stability and in promoting the maturation efficiency of hOAT1. ..
  49. Takahara N, Saga T, Inubushi M, Kusuhara H, Seki C, Ito S, et al. Drugs interacting with organic anion transporter-1 affect uptake of Tc-99m-mercaptoacetyl-triglycine (MAG3) in the human kidney: therapeutic drug interaction in Tc-99m-MAG3 diagnosis of renal function and possible application of Tc-99m-MAG3 for drug . Nucl Med Biol. 2013;40:643-50 pubmed publisher
    ..Drugs with OAT1 affinity affect the renal uptake of Tc-99m-MAG3 and blood clearance. This might cause misinterpretation of functional diagnosis of the kidney using Tc-99m-MAG3. ..
  50. Zlender V, Breljak D, Ljubojevic M, Flajs D, Balen D, Brzica H, et al. Low doses of ochratoxin A upregulate the protein expression of organic anion transporters Oat1, Oat2, Oat3 and Oat5 in rat kidney cortex. Toxicol Appl Pharmacol. 2009;239:284-96 pubmed publisher
  51. Burckhardt B, Henjakovic M, Hagos Y, Burckhardt G. Differential Interaction of Dantrolene, Glafenine, Nalidixic Acid, and Prazosin with Human Organic Anion Transporters 1 and 3. J Pharmacol Exp Ther. 2017;362:450-458 pubmed publisher
    ..At OAT1, more than one binding site must be assumed to explain substrate and drug-dependent stimulation and inhibition of transport activity. ..
  52. Miao Z, Yan S, Wang J, Wang B, Li Y, Xing X, et al. Insulin resistance acts as an independent risk factor exacerbating high-purine diet induced renal injury and knee joint gouty lesions. Inflamm Res. 2009;58:659-68 pubmed publisher
    ..Our data demonstrated strong evidence indicating that insulin resistance acts as an independent risk factor predisposing OLETF rats more susceptible to the development of hyperuricemia and gouty arthritis following high-purine load. ..
  53. Dan H, Peng R, Ao Y, Liu Y. Segment-specific proximal tubule injury in tripterygium glycosides intoxicated rats. J Biochem Mol Toxicol. 2008;22:422-8 pubmed publisher
    ..In summary, we provided evidences supporting that TG caused segment-specific dysfunction in the kidney proximal tubule...
  54. Buist S, Cherrington N, Choudhuri S, Hartley D, Klaassen C. Gender-specific and developmental influences on the expression of rat organic anion transporters. J Pharmacol Exp Ther. 2002;301:145-51 pubmed
    ..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. ..
  55. Nakagawa H, Hirata T, Terada T, Jutabha P, Miura D, Harada K, et al. Roles of organic anion transporters in the renal excretion of perfluorooctanoic acid. Basic Clin Pharmacol Toxicol. 2008;103:1-8 pubmed publisher
    ..Collectively, the difference between the perfluorooctanoic acid half-lives in human beings and rats is not likely to be attributable to differences in the affinities of these transporters for perfluorooctanoic acid. ..
  56. Rizwan A, Krick W, Burckhardt G. The chloride dependence of the human organic anion transporter 1 (hOAT1) is blunted by mutation of a single amino acid. J Biol Chem. 2007;282:13402-9 pubmed
    ..We conclude that Arg(466) influences the binding of glutarate, but not interaction with PAH, and interacts with chloride, which is a major determinant in substrate translocation. ..
  57. Sai Y, Kato Y, Nakamura K, Kato S, Nishimura T, Kubo Y, et al. Carrier-mediated hepatic uptake of a novel nonrenal excretion type uric acid generation inhibitor, Y-700. J Pharm Sci. 2006;95:336-47 pubmed
  58. Burckhardt B, Burckhardt G. Transport of organic anions across the basolateral membrane of proximal tubule cells. Rev Physiol Biochem Pharmacol. 2003;146:95-158 pubmed
    ..The driving forces for OAT2 and OAT3, the relative contributions of all OA transporters to, and the impact of transporter regulation by protein kinases on renal drug excretion in vivo must be determined in future experiments. ..
  59. Enomoto A, Takeda M, Taki K, Takayama F, Noshiro R, Niwa T, et al. Interactions of human organic anion as well as cation transporters with indoxyl sulfate. Eur J Pharmacol. 2003;466:13-20 pubmed
    ..In addition, it was suggested that human-OAT1 and human-OAT3 are involved in the urinary excretion of indoxyl sulfate, the exacerbation of renal dysfunction and the induction of uremic encephalopathy by indoxyl sulfate. ..
  60. Quaglia N, Brandoni A, Ferri A, Torres A. Early manifestation of nephropathy in rats with arterial calcinosis. Ren Fail. 2003;25:355-66 pubmed
    ..It is important to mention that the decrease in clearance of organic anions were seen in spite of the increase in expression of OAT1. ..
  61. Barros S, Srimaroeng C, Perry J, Walden R, Dembla Rajpal N, Sweet D, et al. Activation of protein kinase Czeta increases OAT1 (SLC22A6)- and OAT3 (SLC22A8)-mediated transport. J Biol Chem. 2009;284:2672-9 pubmed publisher
    ..These data demonstrate that PKCzeta activation up-regulates OAT1 and OAT3 function, and that protein-protein interactions play a central role controlling these two important renal drug transporters. ..
  62. Uwai Y, Taniguchi R, Motohashi H, Saito H, Okuda M, Inui K. Methotrexate-loxoprofen interaction: involvement of human organic anion transporters hOAT1 and hOAT3. Drug Metab Pharmacokinet. 2004;19:369-74 pubmed
    ..Their inhibition concentrations (IC(50)) were in the range of the therapeutic levels. These findings suggest that loxoprofen retards the elimination of methotrexate, at least in part, by inhibiting hOAT1 and hOAT3. ..
  63. Hong M, Zhou F, You G. Critical amino acid residues in transmembrane domain 1 of the human organic anion transporter hOAT1. J Biol Chem. 2004;279:31478-82 pubmed
  64. Abe T, Suzuki T, Unno M, Tokui T, Ito S. Thyroid hormone transporters: recent advances. Trends Endocrinol Metab. 2002;13:215-20 pubmed
    ..Here, we discuss the classification of thyroid hormone transporters, with emphasis on how they are influenced by their ionic milieu and what their symported organic anions are. ..
  65. Sharma K, Karl B, Mathew A, Gangoiti J, Wassel C, Saito R, et al. Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease. J Am Soc Nephrol. 2013;24:1901-12 pubmed publisher
    ..We conclude that urine metabolomics is a reliable source for biomarkers of diabetic complications, and our data suggest that renal organic ion transport and mitochondrial function are dysregulated in diabetic kidney disease. ..
  66. Uwai Y, Honjo E. Transport of xanthurenic acid by rat/human organic anion transporters OAT1 and OAT3. Biosci Biotechnol Biochem. 2013;77:1517-21 pubmed
    ..83 µM and 26.0 pmol/oocyte/h respectively. In rOAT3, the respective values were 6.87 µM and 21.7 pmol/oocyte/h. This is the first report on xanthurenic acid transport by OAT1 and OAT3. ..
  67. Shi Y, Wang C, Liu L, Liu Y, Wang X, Hong Y, et al. Antihyperuricemic and nephroprotective effects of resveratrol and its analogues in hyperuricemic mice. Mol Nutr Food Res. 2012;56:1433-44 pubmed publisher
    ..The number and position, methoxylation and glycosylation of hydroxyl groups in these trans-stilbenes were required for their effects. ..
  68. Vallon V, Eraly S, Rao S, Gerasimova M, Rose M, Nagle M, et al. A role for the organic anion transporter OAT3 in renal creatinine secretion in mice. Am J Physiol Renal Physiol. 2012;302:F1293-9 pubmed publisher
    ..The results are consistent with a contribution of OAT3 and possibly OAT1 to renal creatinine secretion in mice. ..
  69. Pacyniak E, Hagenbuch B, Klaassen C, Lehman McKeeman L, Guo G. Organic anion transporting polypeptides in the hepatic uptake of PBDE congeners in mice. Toxicol Appl Pharmacol. 2011;257:23-31 pubmed publisher
    ..In contrast, Oatp2b1 transported all three PBDE congeners with similar affinities. The importance of hepatic Oatps for the liver accumulation of BDE47 was confirmed using Oatp1a4-, and Oatp1b2-null mice. ..
  70. Zhang R, Yang X, Li J, Wu J, Peng W, Dong X, et al. Upregulation of rat renal cortical organic anion transporter (OAT1 and OAT3) expression in response to ischemia/reperfusion injury. Am J Nephrol. 2008;28:772-83 pubmed publisher
  71. Ogasawara K, Terada T, Motohashi H, Asaka J, Aoki M, Katsura T, et al. Analysis of regulatory polymorphisms in organic ion transporter genes (SLC22A) in the kidney. J Hum Genet. 2008;53:607-14 pubmed publisher
    ..This is the first study to investigate the influences of rSNPs on mRNA expression of SLC22A in the kidney and to identify a regulatory polymorphism affecting OCT2 promoter activity. ..
  72. Wang C, Wang Y, Wang X, Zhang X, Ye J, Hu L, et al. Mulberroside a possesses potent uricosuric and nephroprotective effects in hyperuricemic mice. Planta Med. 2011;77:786-94 pubmed publisher
    ..These data suggest that mulberroside A may be a new drug candidate for the treatment of hyperuricemia with renal dysfunction. ..
  73. Moss D, Kwan W, Liptrott N, Smith D, Siccardi M, Khoo S, et al. Raltegravir is a substrate for SLC22A6: a putative mechanism for the interaction between raltegravir and tenofovir. Antimicrob Agents Chemother. 2011;55:879-87 pubmed publisher
    ..However, transport was limited compared to endogenous controls, and these transporters are unlikely to have a great impact on raltegravir pharmacokinetics. ..
  74. Bahn A, Ljubojevic M, Lorenz H, Schultz C, Ghebremedhin E, Ugele B, et al. Murine renal organic anion transporters mOAT1 and mOAT3 facilitate the transport of neuroactive tryptophan metabolites. Am J Physiol Cell Physiol. 2005;289:C1075-84 pubmed
    ..Consequently, they are crucial for the regulation of central nervous system tryptophan metabolite concentration. ..
  75. Tahara H, Shono M, Kusuhara H, Kinoshita H, Fuse E, Takadate A, et al. Molecular cloning and functional analyses of OAT1 and OAT3 from cynomolgus monkey kidney. Pharm Res. 2005;22:647-60 pubmed
    ..These results suggest that monkey is a good predictor of the renal uptake of organic anions in the human. ..
  76. Gwak H, Oh J, Han H. Effects of non-steroidal anti-inflammatory drugs on the pharmacokinetics and elimination of aciclovir in rats. J Pharm Pharmacol. 2005;57:393-8 pubmed
    ..Therefore, concomitant use of ketoprofen or naproxen with aciclovir should require close monitoring for clinical consequence of potential drug interaction. ..
  77. Xu F, Li Z, Zheng J, Gee Cheung F, Chan T, Zhu L, et al. The inhibitory effects of the bioactive components isolated from Scutellaria baicalensis on the cellular uptake mediated by the essential solute carrier transporters. J Pharm Sci. 2013;102:4205-11 pubmed publisher
  78. Hong M, Xu W, Yoshida T, Tanaka K, Wolff D, Zhou F, et al. Human organic anion transporter hOAT1 forms homooligomers. J Biol Chem. 2005;280:32285-90 pubmed
    ..Taken together, this is the first study demonstrating that hOAT1 exists in the plasma membrane as a homooligomer, possibly trimer, and higher order of oligomer. ..
  79. Stray K, Bam R, Birkus G, Hao J, Lepist E, Yant S, et al. Evaluation of the effect of cobicistat on the in vitro renal transport and cytotoxicity potential of tenofovir. Antimicrob Agents Chemother. 2013;57:4982-9 pubmed publisher
    ..These results illustrate that COBI and TFV interact primarily with distinct renal transporters and indicate a low potential for pharmacokinetic renal drug-drug interaction. ..
  80. Schneider R, Meusel M, Renker S, Bauer C, Holzinger H, Roeder M, et al. Low-dose indomethacin after ischemic acute kidney injury prevents downregulation of Oat1/3 and improves renal outcome. Am J Physiol Renal Physiol. 2009;297:F1614-21 pubmed publisher
    ..In accordance to the decreased PAH net secretion, renal excretion of an endogenous organic anion (PGE(2)) is also impaired after ischemia and reperfusion...
  81. Wolman A, Gionfriddo M, Heindel G, Mukhija P, Witkowski S, Bommareddy A, et al. Organic anion transporter 3 interacts selectively with lipophilic ?-lactam antibiotics. Drug Metab Dispos. 2013;41:791-800 pubmed publisher
    ..These findings indicate that Oat3 recognizes lipophilic ?-lactams more readily. Moreover, this study has potential implications for designing ?-lactams to avoid renal accumulation or brain efflux via Oat3. ..
  82. Wong C, Barron D, Orfila C, Dionisi F, Krajcsi P, Williamson G. Interaction of hydroxycinnamic acids and their conjugates with organic anion transporters and ATP-binding cassette transporters. Mol Nutr Food Res. 2011;55:979-88 pubmed publisher
    ..Concerted action of OAT1, OAT3, and OAT4 is involved in the elimination of hydroxycinnamic acid conjugates into urine, whereas MRP2 and breast cancer resistance protein are not involved in the disposition of these conjugates. ..
  83. Zhang Q, Li S, Patterson C, You G. Lysine 48-linked polyubiquitination of organic anion transporter-1 is essential for its protein kinase C-regulated endocytosis. Mol Pharmacol. 2013;83:217-24 pubmed publisher
    ..Together, our findings demonstrate for the first time that Lys48-linked polyubiquitination is essential for PKC-regulated OAT1 trafficking. ..
  84. Imamura Y, Murayama N, Okudaira N, Kurihara A, Inoue K, Yuasa H, et al. Effect of the fluoroquinolone antibacterial agent DX-619 on the apparent formation and renal clearances of 6?-hydroxycortisol, an endogenous probe for CYP3A4 inhibition, in healthy subjects. Pharm Res. 2013;30:447-57 pubmed publisher
    ..Caution is needed in applying CL(6?-OHF) as an index of hepatic CYP3A4 activity without evaluating CL(renal,6?-OHF). ..
  85. Villar S, Brandoni A, Quaglia N, Torres A. Renal elimination of organic anions in rats with bilateral ureteral obstruction. Biochim Biophys Acta. 2004;1688:204-9 pubmed
    ..The diminished Na,K-ATPase activity in cortex from obstructed kidneys might condition OAT1 function. Additionally, it is also possible to conclude that in the presence of BUO, PAH clearance is not a good estimate of renal plasma flow. ..
  86. Lou Y, Li J, Lu Y, Wang X, Jiao R, Wang S, et al. Aristolochic acid-induced destruction of organic ion transporters and fatty acid metabolic disorder in the kidney of rats. Toxicol Lett. 2011;201:72-9 pubmed publisher
  87. Ahn S, Jamshidi N, Mo M, Wu W, Eraly S, Dnyanmote A, et al. Linkage of organic anion transporter-1 to metabolic pathways through integrated "omics"-driven network and functional analysis. J Biol Chem. 2011;286:31522-31 pubmed publisher
    ..Y., and Nigam, S. K. (2009) Mol. Pharmacol. 76, 481-490, and Wu, W., Dnyanmote, A. V., and Nigam, S. K. (2011) Mol. Pharmacol. 79, 795-805). Drugs may alter metabolism by competing for OAT1 binding of metabolites. ..
  88. Srimaroeng C, Chatsudthipong V, Aslamkhan A, Pritchard J. Transport of the natural sweetener stevioside and its aglycone steviol by human organic anion transporter (hOAT1; SLC22A6) and hOAT3 (SLC22A8). J Pharmacol Exp Ther. 2005;313:621-8 pubmed
    ..In conclusion, stevioside had no interaction with either hOAT1 or hOAT3, whereas hOAT1, hOAT3, and fOat1 were all shown to be capable of steviol transport and thus, can play a role in its renal transport and excretion. ..