Organic anion transporter

Thank you for visiting nature.

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.

Organic anion transporter

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. Inhibition of OATs is used therapeutically to improve drug efficacy and reduce nephrotoxicity. However, the mechanisms linking metabolite cycling, drug transport and intracellular chloride remain obscure. Organic anions comprise a large group of endogenous and exogenous compounds, including tricarboxylic acid intermediates, bile acids, prostaglandins, fatty acids, anionic drugs and environmental toxins. Many organic anions result from the breakdown of metabolites, such as nucleic and amino acids, and must be cleared from the body to avoid accumulation and toxicity 1 , 2. The transport of organic anions across the cell membrane is mediated by the organic anion transporters OATs , the organic anion transporting polypeptides OATPs and the multidrug resistance-associated family of ATP-driven transporters 3 , 4 , 5.

Cereghini S.

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.

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.

Organic anion transporter

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.

Very faint line on clear blue

Some of the Slc22 family organic anion transporters have an extremely high percentage of sequence identity. Acute regulation of OAT3-mediated estrone sulfate transport in isolated rabbit renal proximal tubules. HCC is an aggressive malignancy primarily due to tumor metastasis or recurrence, even after potentially curative treatment. Role of organic anion transporter OATP1B1 OATP-C in hepatic uptake of irinotecan and its active metabolite, 7-ethylhydroxycamptothecin: in vitro evidence and effect of single nucleotide polymorphisms. This would lead to an implausible direct polar interaction between the extracellular loop ECL 1 and the intracellular C-terminal domain in the lipid bilayer. Comparison of simple potential functions for simulating liquid water. The absence of a robust h OAT1 OF model precludes the thorough atomistic rationalization of substrate binding events as well as the investigation of lipid-protein interactions, which have been shown to be of major importance for several MFS transporters and other membrane proteins by either experimental or computational techniques 30 , 31 , 32 , A key question in deciphering the mechanism of secondary active transporters is how ligand binding drives the conformational changes in the protein Oat6 can bind conjugated steroids and some drugs, but perhaps most interestingly, it can interact with volatile odorants e. Biochim Biophys Acta : —, Kaback, H. Even though key residues can be identified from computational as well as experimental studies, the dynamic and atomic features of h OAT1 structure still remain unclear 18 , 24 , 28 , 29 see Supplementary Table S1 for details.

Federal government websites often end in. The site is secure.

Metabolomics studies in the knockouts also provide support for the connections of Oats with phase I e. Accepted : 12 April Conflict-of-interest statement: No potential conflicts of interest exist. Although, as mentioned, the Urat1 Rst knockout has a defect in urate handling, it is modest, and at the time, it was suggested that other genes must be important You are using a browser version with limited support for CSS. Gene information is provided for human Hs , mouse Mm and rat Rn. The Oat1 knockout is also defective in the handling of many important metabolites involved in endogenous metabolism Table 2 74 , While there had already been in vitro evidence for the role of Oats, particularly Oat3 and Oat1, in the transport of sulfated and glucuronidated substrates, these were also among the major metabolites among many others found in the Oat1 and Oat3 knockouts , , Close banner Close. Physiol Genomics.