Organic anion transporter

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Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. In mammals, the kidney plays an essential role in maintaining blood homeostasis through the selective uptake, retention or elimination of toxins, drugs and metabolites. Organic anion transporters OATs are responsible for the recognition of metabolites and toxins in the nephron and their eventual urinary excretion.

Organic anion transporter

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human Hs , mouse Mm and rat Rn. Show » « Hide. Organic anion transporters OATs are non-selective transporters prominent in the kidney, placenta and blood-brain barrier. Handb Exp Pharmacol , : Mol Aspects Med , 34 : Annu Rev Pharmacol Toxicol , 58 : Drug Metab Dispos , 45 2 : Drug Metab Dispos , 50 9 : [Epub ahead of print]. Acta Pharm Sin B , 6 5 : J Biol Chem , 6 : Kidney Int , 63 1 :

Crystal structure and mechanism of GlpT, the glycerolphosphate transporter from E. Jiang, D.

Federal government websites often end in. The site is secure. They are expressed in many tissues, such as the liver and kidney, and mediate the absorption and excretion of many endogenous and exogenous substances, including various drugs. Most are composed of 12 transmembrane polypeptide chains with the C-terminus and the N-terminus located in the cell cytoplasm. OATs and OATPs are abundantly expressed in the liver, where they mainly promote the uptake of various endogenous substrates such as bile acids and various exogenous drugs such as antifibrotic and anticancer drugs. However, differences in the locations of glycosylation sites, phosphorylation sites, and amino acids in the OAT and OATP structures lead to different substrates being transported to the liver, which ultimately results in their different roles in the liver. To date, few articles have addressed these aspects of OAT and OATP structures, and we study further the similarities and differences in their structures, tissue distribution, substrates, and roles in liver diseases.

Members of the Organo Anion Transporter OAT Family organic-anion-transporting polypeptides , OATP are membrane transport proteins or 'transporters' that mediate the transport of mainly organic anions across the cell membrane. Therefore, OATPs are present in the lipid bilayer of the cell membrane, acting as the cell's gatekeepers. Organic anion transporting polypeptides carry bile acids as well as bilirubin and numerous hormones such as thyroid and steroid hormones across the basolateral membrane facing sinusoids in hepatocytes , for excretion in bile. They also transport an extremely diverse range of drug compounds, ranging from anti-cancer, antibiotic, lipid lowering to anti-diabetic drugs, as well as toxins and poisons. They also transport the dye bromosulphopthalein , availing it as a liver-testing substance. The various paralogues in a mammal have differing but overlapping substrate specificities and tissue distributions as summarized by Hagenbuch and Meier. OAT family homologues have been found in other animals but not outside of the animal kingdom. These transporters have been characterized in mammals, but homologues are present in Drosophila melanogaster , Anopheles gambiae , and Caenorhabditis elegans.

Organic anion transporter

Federal government websites often end in. The site is secure. The organic anion transporter OAT subfamily, which constitutes roughly half of the SLC22 solute carrier 22 transporter family, has received a great deal of attention because of its role in handling of common drugs antibiotics, antivirals, diuretics, nonsteroidal anti-inflammatory drugs , toxins mercury, aristolochic acid , and nutrients vitamins, flavonoids. Oats are expressed in many tissues, including kidney, liver, choroid plexus, olfactory mucosa, brain, retina, and placenta. Recent metabolomics and microarray data from Oat1 [ Slc22a6 , originally identified as NKT novel kidney transporter ] and Oat3 Slc22a8 knockouts, as well as systems biology studies, indicate that this pathway plays a central role in the metabolism and handling of gut microbiome metabolites as well as putative uremic toxins of kidney disease. Oats may also play a major role in interorganismal communication via movement of small molecules across the intestine, placental barrier, into breast milk, and volatile odorants into the urine. The role of various Oat isoforms in systems physiology appears quite complex, and their ramifications are discussed in the context of remote sensing and signaling. Modeling, mutagenesis, and other studies are consistent with the view that these transmembrane proteins are composed of about — amino acids comprising 12 transmembrane domains 69 , , , Figure 1.

Strippoker at the inventory

About this article. Human OAT1 [ ] and OAT2 [ ] promoter activities are increased by another liver-enriched transcription factor: HNF-4a, which is in the nuclear receptor family and is known to have an indispensable role in hepatocyte differentiation and the maintenance of liver gene expression. Knockouts of Urat1 Rst , as well as knockouts of Oat1 and Oat3 , have alterations in urate handling 73 , Insights into the mechanism of action of cidofovir and other acyclic nucleoside phosphonates against polyoma- and papillomaviruses and non-viral induced neoplasia. Molecular identification of a renal urate anion exchanger that regulates blood urate levels. There are, however, striking parallels between kidney development and kidney recovery after injury. Ito S, Alcorn J. This requires quantitative data from different cell types and perhaps real time measurements of small molecules. Modulation of OATP1B-type transporter function alters cellular uptake and disposition of platinum chemotherapeutics. Relationships between hemodynamic alterations and Child-Pugh Score in patients with cirrhosis.

OAT1 is a transmembrane protein that is expressed in the brain, the placenta, the eyes, smooth muscles , and the basolateral membrane of proximal tubular cells of the kidneys. It plays a central role in renal organic anion transport. Along with OAT3 , OAT1 mediates the uptake of a wide range of relatively small and hydrophilic organic anions from plasma into the cytoplasm of the proximal tubular cells of the kidneys.

In addition, ex vivo transport assays using knockout kidney and choroid plexus indicate a defect in handling antiviral drugs , , Expression and function of Oat1 and Oat3 in rat kidney exposed to mercuric chloride. Oats, intracellular concentrations of metabolites and signaling molecules, and possible connections to organellar small molecule transporters Drugs and toxins enter the proximal tubule cell by Oat1 and Oat3 and, in some cases, cause such as the instances of cephaloridine and mercury toxicity to the proximal tubule cell 21 , Oats and other multispecific transporters may have evolved in part to handle exogenous toxins, but their physiological role seems to be regulation of metabolite and signaling pathways see sect. Case, D. Indeed, Oat-PG appears to be highly specific for prostaglandin substrates Lipids modulate the conformational dynamics of a secondary multidrug transporter. Schuppan D, Afdhal NH. Publish with us For authors Language editing services Submit manuscript. Convergence of Wnt signaling on the HNF4alpha-driven transcription in controlling liver zonation. Entecavir, a guanosine cyclopentanoate analog, is a first-line drug used for hepatitis B and has a significant effect against hepatitis B virus HBV by inhibiting HBV polymerase[ 77 ]. Japan Pharmaceutical and Medical Devices Agency. Although their most likely role seems to be in the transport of organic molecules, it is also conceivable that they have a role in an independent transport function[ 20 ].