SLC22A8

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Solute carrier family 22 (organic anion transporter), member 8
Identifiers
Symbols SLC22A8 ; OAT3
External IDs OMIM607581 MGI1336187 HomoloGene20901 IUPHAR: 1027 ChEMBL: 1641348 GeneCards: SLC22A8 Gene
RNA expression pattern
PBB GE SLC22A8 221298 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 9376 19879
Ensembl ENSG00000149452 ENSMUSG00000063796
UniProt Q8TCC7 O88909
RefSeq (mRNA) NM_001184732 NM_001164634
RefSeq (protein) NP_001171661 NP_001158106
Location (UCSC) Chr 11:
62.76 – 62.78 Mb
Chr 19:
8.59 – 8.61 Mb
PubMed search [1] [2]

Solute carrier family 22 member 8 is a protein that in humans is encoded by the SLC22A8 gene.[1][2][3]

Function[edit]

This protein is also called organic anion transporter 3 (OAT3). It is involved in the transport and excretion of organic ions some of which are drugs (e.g., penicillin G (benzylpenicillin), methotrexate (MTX), indomethacin (an NSAID), ciprofloxacin (a carboxyfluoroquinolone), and some of which are pure toxicants.[2] SLC22A8 (OAT3) is indirectly dependent on the inward sodium gradient, which is a driving force for reentry of dicarboxylates into the cytosol. Dicarboxylates, such as alpha-ketoglutarate generated within the cell, or recycled from the extracellular space, are used as exchange substrates to fuel the influx of organic anions against their concentration gradient. The encoded protein is an integral membrane protein and appears to be localized to the basolateral membrane of renal proximal tubule cells.[3]

References[edit]

  1. ^ Race JE, Grassl SM, Williams WJ, Holtzman EJ (1999). "Molecular Cloning and Characterization of Two Novel Human Renal Organic Anion Transporters (hOAT1 and hOAT3)". Biochemical and Biophysical Research Communications 255 (2): 508–14. doi:10.1006/bbrc.1998.9978. PMID 10049739. 
  2. ^ a b VanWert AL, Gionfriddo MR, Sweet DH (2009). "Organic anion transporters: Discovery, pharmacology, regulation and roles in pathophysiology". Biopharmaceutics & Drug Disposition: n/a. doi:10.1002/bdd.693. PMID 19953504. 
  3. ^ a b EntrezGene 9376

Further reading[edit]

  • Babu E, Takeda M, Narikawa S, Kobayashi Y, Yamamoto T, Cha SH et al. (2002). "Human Organic Anion Transporters Mediate the Transport of Tetracycline". The Japanese Journal of Pharmacology 88 (1): 69–76. doi:10.1254/jjp.88.69. PMID 11855680. 
  • Motohashi H, Sakurai Y, Saito H, Masuda S, Urakami Y, Goto M et al. (2002). "Gene expression levels and immunolocalization of organic ion transporters in the human kidney". Journal of the American Society of Nephrology 13 (4): 866–74. PMID 11912245. 
  • Nishizato Y, Ieiri I, Suzuki H, Kimura M, Kawabata K, Hirota T, Takane H, Irie S et al. (2003). "Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: Consequences for pravastatin pharmacokinetics". Clinical Pharmacology & Therapeutics 73 (6): 554–65. doi:10.1016/S0009-9236(03)00060-2. PMID 12811365. 
  • Bakhiya A, Bahn A, Burckhardt G, Wolff N (2003). "Human Organic Anion Transporter 3 (hOAT3) can Operate as an Exchanger and Mediate Secretory Urate Flux". Cellular Physiology and Biochemistry 13 (5): 249–56. doi:10.1159/000074539. PMID 14586168. 
  • Sakurai Y, Motohashi H, Ueo H, Masuda S, Saito H, Okuda M, Mori N, Matsuura M et al. (2004). "Expression Levels of Renal Organic Anion Transporters (OATs) and Their Correlation with Anionic Drug Excretion in Patients with Renal Diseases". Pharmaceutical Research 21 (1): 61–7. doi:10.1023/B:PHAM.0000012153.71993.cb. PMID 14984259. 
  • Srimaroeng C, Chatsudthipong V, Aslamkhan AG, Pritchard JB (2004). "Transport of the Natural Sweetener Stevioside and Its Aglycone Steviol by Human Organic Anion Transporter (hOAT1; SLC22A6) and hOAT3 (SLC22A8)". Journal of Pharmacology and Experimental Therapeutics 313 (2): 621–8. doi:10.1124/jpet.104.080366. PMID 15644426. 
  • Tahara H, Shono M, Kusuhara H, Kinoshita H, Fuse E, Takadate A et al. (2005). "Molecular Cloning and Functional Analyses of OAT1 and OAT3 from Cynomolgus Monkey Kidney". Pharmaceutical Research 22 (4): 647–60. doi:10.1007/s11095-005-2503-0. PMID 15846473. 
  • Erdman AR, Mangravite LM, Urban TJ, Lagpacan LL, Castro RA, de la Cruz M, Chan W, Huang CC et al. (2005). "The human organic anion transporter 3 (OAT3; SLC22A8): Genetic variation and functional genomics". AJP: Renal Physiology 290 (4): F905–12. doi:10.1152/ajprenal.00272.2005. PMID 16291576. 
  • Tahara H, Kusuhara H, Maeda K, Koepsell H, Fuse E, Sugiyama Y (2006). "Inhibition of Oat3-Mediated Renal Uptake As a Mechanism for Drug-Drug Interaction Between Fexofenadine and Probenecid". Drug Metabolism and Disposition 34 (5): 743–7. doi:10.1124/dmd.105.008375. PMID 16455804. 
  • Bhatnagar V, Xu G, Hamilton BA, Truong DM, Eraly SA, Wu W et al. (2006). "Analyses of 5′ regulatory region polymorphisms in human SLC22A6 (OAT1) and SLC22A8 (OAT3)". Journal of Human Genetics 51 (6): 575–80. doi:10.1007/s10038-006-0398-1. PMID 16648942. 
  • Kikuchi R, Kusuhara H, Hattori N, Shiota K, Kim I, Gonzalez FJ et al. (2006). "Regulation of the Expression of Human Organic Anion Transporter 3 by Hepatocyte Nuclear Factor 1 /beta and DNA Methylation". Molecular Pharmacology 70 (3): 887–96. doi:10.1124/mol.106.025494. PMID 16793932. 
  • Mizuno N, Takahashi T, Iwase Y, Kusuhara H, Niwa T, Sugiyama Y (2007). "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 Metabolism and Disposition 35 (8): 1429–34. doi:10.1124/dmd.106.013912. PMID 17502342. 
  • Matsumoto S, Yoshida K, Ishiguro N, Maeda T, Tamai I (2007). "Involvement of Rat and Human Organic Anion Transporter 3 in the Renal Tubular Secretion of Topotecan [(S)-9-Dimethylaminomethyl-10-hydroxy-camptothecin hydrochloride]". Journal of Pharmacology and Experimental Therapeutics 322 (3): 1246–52. doi:10.1124/jpet.107.123323. PMID 17556638. 
  • Nozaki Y, Kusuhara H, Kondo T, Iwaki M, Shiroyanagi Y, Nakayama H, Horita S, Nakazawa H et al. (2007). "Species Difference in the Inhibitory Effect of Nonsteroidal Anti-Inflammatory Drugs on the Uptake of Methotrexate by Human Kidney Slices". Journal of Pharmacology and Experimental Therapeutics 322 (3): 1162–70. doi:10.1124/jpet.107.121491. PMID 17578901. 
  • Vanwert AL, Bailey RM, Sweet DH (2007). "Organic anion transporter 3 (Oat3/Slc22a8) knockout mice exhibit altered clearance and distribution of penicillin G". AJP: Renal Physiology 293 (4): F1332–41. doi:10.1152/ajprenal.00319.2007. PMC 2820253. PMID 17686950. 
  • VanWert AL, Sweet DH (2007). "Impaired Clearance of Methotrexate in Organic Anion Transporter 3 (Slc22a8) Knockout Mice: A Gender Specific Impact of Reduced Folates". Pharmaceutical Research 25 (2): 453–62. doi:10.1007/s11095-007-9407-0. PMC 2820254. PMID 17660957. 
  • Windass AS, Lowes S, Wang Y, Brown CD (2007). "The Contribution of Organic Anion Transporters OAT1 and OAT3 to the Renal Uptake of Rosuvastatin". Journal of Pharmacology and Experimental Therapeutics 322 (3): 1221–7. doi:10.1124/jpet.107.125831. PMID 17585018.