Organic anion transporter

Unless otherwise stated all data on this page refer to the human proteins.

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.

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. Furthermore, OAT1 is also involved in key physiological events such as the remote inter-organ communication. Despite its significance, the knowledge about h OAT1 structure and the transport mechanism at the atomic level remains fragmented owing to the lack of resolved structures. Taking advantage of the AlphaFold 2 predicted structure of h OAT1 in inward-facing conformation, we here provide the essential structural and functional features comparing both states. The principal element of the event points at interactions of charged residues that appear crucial for the transporter dynamics and function. Moreover, h OAT1 model was embedded in different lipid bilayer membranes highlighting the crucial structural dependence on lipid-protein interactions. MD simulations supported the pivotal role of phosphatidylethanolamine components to the protein conformation stability.

All systems were solvated in water and neutralized with mM NaCl ions to match physiological conditions. Clin Pharmacokinet.

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. From there, these substrates are transported into the lumen of the nephrons of the kidneys for excretion. OAT1 homologs have been identified in rats , mice , rabbits , pigs , flounders , and nematodes.

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. A: illustration of the predicted topology of organic anion transporters. Although the initial focus in this field was on the kidney, the OATs have been localized to almost all barrier epithelia of the body, as well as endothelium and other cells, and have demonstrated roles in the regulated transcellular movement of numerous small organic anionic molecules across these epithelial barriers and between body fluid compartments i.

Organic anion transporter

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.

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Schuppan D, Afdhal NH. Novel aspects of renal organic anion transporters. Nat Genet 33 Suppl : —, Similar to other SLC transporter subfamilies, many members of the SLC22 family, such as OAT1 and OAT3, are highly conserved, and their orthologs can often be found in most vertebrate species as well as fly and worm 70 , This points to limitations in the nomenclature of organic anion transporters which, as was originally suggested , are able to transport many organic anions and some organic cations. Thus, at least in the mouse genome, Oats may still be under active selection. This would have potentially important clinical applications and is of obvious relevance in the context of the Remote Sensing and Signaling Hypothesis 5 , Both of these drugs must be phosphorylated by host enzymes before they become active. Wu, W. Studies have demonstrated that Oat1 and Oat3 mRNA levels are regulated not only during development but also in response to various physiological and pathophysiological stimuli toxins, growth factors, and various hormones. Chr Organic anion and cation transporters occur in pairs of similar and similarly expressed genes.

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.

Nevertheless, based on its localization and putative transport function, it has been suggested that Oat6 could modulate the bioavailability of the odorant stimulus to olfactory neurons There is also a group of transporters that is sometimes referred to as the Flipt fly-like putative transporter and CT carnitine transporter ; while their main function may be in carnitine transport, these transporters have not been studied in sufficient detail 16 , The hypothesis may facilitate building a new framework for novel avenues of molecular, cellular, and physiological experimentation and analysis of large data sets in the field, as well as reevaluation of older studies in a systems biology context. Single-dose pharmacokinetics of repaglinide in subjects with chronic liver disease. Galochkina, T. This would have potentially important clinical applications and is of obvious relevance in the context of the Remote Sensing and Signaling Hypothesis 5 , Deng, D. A high-affinity sybody with a slow off rate, as measured using biolayer interferometry Octet Red , was identified from the concave library. USA , E—E Indinavir is a protease inhibitor and works by a different mechanism than the other antiviral drugs. All reasonable requests for source data will be actioned with an appropriate MTA. Supplementary Information. Gender is an important factor in their expression patterns Many drugs are organic anions and thus concentrated in renal cells via SLC22 family members 12 , often resulting in adverse drug—drug interactions DDI and increased elimination 13 , 14 , 15 , 16 ,