The sulfate permease sulp family is a member of the large apc superfamily of secondary carriers. The present study investigated whether or not nonsteroidal antiinflammatory drugs nsaids are transported by oat1. Common to oat1, oat2, and oat3 is their ability to transport cgmp. Nas1 sulfate transporter,hyposulfataemia and autism 1 h. Lamotrigine, tablet, 200 mg1, oral, torrent pharmaceuticals limited, 20090127, not applicable, us us. Phylogentically, organic anion transporter oat1 and oat3 are closely related, whereas oat2 is more distant. Lopid gemfibrozil tablets, usp is indicated as adjunctive therapy to diet for.
Expression profiling of solute carrier gene families at. The sulfate transporter is a solute carrier family protein that in humans is encoded by the slc26a2 gene. First isolated in 1997 from rat kidney using xenopus oocyte expression assay, organic anion transporter 1 oat1 was demonstrated to mediate the accumulation of paminohippurate, the prototypical organic anion used to study renal organic anion transport sekine et al. In kidney, oats are responsible for extracting potentially toxic endogenous and exogenous molecules from plasma and delivering them to the tubular lumen for excretion in urine. Nas1 and sat1 encode renal anion transporters that mediate proximal tubular sulfate reabsorption and thereby regulate blood sulfate levels. Structural basis for amino acid transport by the cat family of slc7. Absence of the sulfate transporter sat1 has no impact on. Slc3a2 4f2hc for insertion into the plasma membrane torrents et al. Distribution of expression profiles for slc genes in the choroid plexus cp. Organic anion transporter 4 organic anion transporters. Organic anion transporters and their implications in. Na independent neutral amino acid transporter lat1.
James,c niels sandal,d jens stougaard,d masayoshi kawaguchi,e ai miyamoto,f norio suganuma,f and michael k. Organic anion transporter 1 how is organic anion transporter 1 abbreviated. Organic anion transporter 3 and organic anion transporting polypeptides 1b1 and 1b3mediated transport of catalposide hyeonuk jeong,1 mihwa kwon,2 yongnam lee,3 ji seok yoo,3 dae hee shin,3 imsook song,2 hye suk lee1 1college of pharmacy, the catholic university of korea, bucheon 420743, korea. Slco1a2 solute carrier organic anion transporter family member 1a2, authors. Organic anion transporter 1 is inhibited by multiple mechanisms and shows a transport mode independent of exchanges adam g. Novel liverspecific organic anion transporter oat7 that operates the. Chondroitin sulfate, lamotrigine may decrease the excretion rate of chondroitin.
Organic anion transporter 1 oat1,9,10 a gene originally identified as novel kidney transporter nkt and proposed to function in organic ion received february, 2008. Slc21a9, which transports estrone3sulfate,38,39 has been reported to be. Pelis department of pharmacology, dalhousie university, halifax, nova scotia, canada received may 27, 2015. Human oat1 was found to be expressed predominantly in the kidney and only weakly in the brain. Both tm1 and tm6 are broken in the centre of the transporter to form. If slc26a11 regulates sulfate availability in the csf, it may. Zou l, stecula a, gupta a, prasad b, chien hc, yee sw, wang l, unadkat jd, stahl sh, fenner ks, giacomini km. Cao mj1, wang z, wirtz m, hell r, oliver dj, xiang cb. A threedimensional model of human organic anion transporter 1. Many organisms including bacillus subtilis, synechocystis sp, saccharomyces cerevisiae, arabidopsis thaliana and caenorhabditis elegans possess multiple sulp family paralogues. A, transportermediated clearance of 3 hlabeled estrone 3sulfate es, cimetidine, and 1mpp was calculated as the clearance in injected oocytes minus the clearance of uninjected oocytes. Sulphate abc transporter, permease protein cysw ipr011866. Often, renal adverse effects are recognized only during clinical stages of drug development. All of the nsaids tested inhibited 14cpah uptake via oat1 expressed in xenopus laevis oocytes.
Slc26a11 sodiumindependent sulfate anion transporter homo. Relevance of copper transporter 1 and organic cation. Transport of estrone 3sulfate mediated by organic anion transporter. It plays a key role in the disposition and hepatic clearance of mostly cationic drugs and endogenous compounds. Borsani g, reig n, fernandez e, estevez r, pineda m, torrents d, camps m, lloberas j, zorzano a, palacin m september 1999. Characterization of the human sulfate anion transporter hsat1. Molybdate transport through the plant sulfate transporter. Organic cation transporter 2 oct2 straight healthcare. Human organic anion transporter 1oat1 encodes a 563 amino acid residue protein, and which is predicted 12 putative membranespanning protein. Characterization of the human sulfate anion transporter hsat1 protein and gene sat1.
The anion exchanger sat1 sulfate anion transporter 1 slc26a1 is considered an important regulator of oxalate and sulfate homeostasis, but the mechanistic basis of these critical roles remain undetermined. A canalicular multispecific organic anion transporter 1 that is encoded in the genome of human. Organic cation transporter 1 how is organic cation. Organic anion transporter 4 organic anion transporters oats. Druginduced nephrotoxicity still hampers drug development, because current translation from in vitro or animal studies to human lacks high predictivity. Looking for online definition of organic anion transporter f in the medical dictionary. Slco1b3 belongs to the organic anion transporter oatp family. Organic anion transporter polypeptiderelated protein 1. Slco3a1 solute carrier organic anion transporter family member 3a1 chlorocebus sabaeus african green monkey. Transporter function and protein expression were assessed in oatp1a2transfected hek293 cells that coexpressed pdzk1 or nherf1. Information and translations of organic anion transporters, sodiumindependent in the most comprehensive dictionary definitions resource.
This gene is a member of a family of sulfateanion transporter genes. Members of the organic anion transporter oat 2 family mediate transport of anionic drugs, toxins, and other xenobiotics across excretory and barrier tissues. Substrate estrone3sulfate uptake by oatp1a2 was significantly increased to. The aim of this study was to investigate the relevance of copper transporter 1 ctr1 and organic cation transporters oct for oxaliplatin uptake and resistance to the drug in sensitive and oxaliplatinresistant ileocecal colorectal adenocarcinoma cells. Identification of a membrane protein, lat2, that coexpresses with. Small molecular drug transfer across the bloodbrain barrier via. Transport of estrone 3sulfate mediated by organic anion transporter oatp4c1. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool. Interactions of human organic anion as well as cation. Slc26a1 gene genecards s26a1 protein s26a1 antibody. Interpro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. Slc26a1 solute carrier family 26 member 1 is a protein coding gene. Ion transporter synonyms, ion transporter pronunciation, ion transporter translation, english dictionary definition of ion transporter.
These primary transporters are enzymes that convert energy from various sourcesincluding adenosine triphosphate atp, sunlight, and other redox reactionsto potential energy stored in an electrochemical gradient. Major role of organic anion transporter 3 in the transport of indoxyl sulfate in the kidney article in kidney international 615. Interaction of organic cations with organic anion transporters. Molybdate transport through the plant sulfate transporter shst1.
Definition of organic anion transporters, sodiumindependent in the dictionary. Organic anion transporter 1 is inhibited by multiple. Sat1 null mice also exhibit hyperoxalemia, hyperoxaluria and calcium oxalate urolithiasis. Organic anion transporter f definition of organic anion. Circulating sulfate levels are maintained by the nas1 sulfate transporter,which is expressed in the kidneywhere it facilitates renal sulfate reabsorption. We couldnt find direct synonyms for the term organic cation transporter 1. Treatment of adult patients with very high elevations of serum triglyceride levels types iv and v hyperlipidemia who present a risk of pancreatitis and who do not respond adequately to a determined dietary effort to control them.
Hotchkiss, tiandai gao, usman khan, liam berrigan, mansong li, leslie ingraham, and ryan m. The expression and activity of these transporters is influenced by several conditions, including transcriptional regulation, genderdependent regulation, and genetic variation. The sulfate transporter sst1 is crucial for symbiotic. Pineda m, fernandez e, torrents d, estevez r, lopez c, camps. Protein ontology mediates hepatobiliary excretion of numerous organic anions and conjugated organic anions such as methotrexate, 17betaestradiol 17glucosiduronic acid and leukotriene c4 pmid. Effects of indoxyl sulfate on organic anion uptake mediated by humanoats and ratoat2, and organic cation uptake mediated by humanocts. Come and experience your torrent treasure chest right here. Physiological roles of mammalian sulfate transporters nas1. Oatps are involved in the membrane transport of bile acids, conjugated steroids, thyroid hormone, eicosanoids, peptides, and numerous drugs in many tissues mikkaichi et al. The measurements were performed in a single experiment using the same group of oocytes. It is a member of the organic anion transporter oat family of proteins. Family members are well conserved in their genomic number and size of.
Novel liverspecific organic anion transporter oat7 that operates the exchange of sulfate conjugates for short chain fatty acid butyrate. Review of organic cation transporter 2 oct2 including list of inducers, inhibitors, and substrates. Family members are well conserved in their genomic number and size of exons and protein aa length among species structures, but have markedly different tissue expression patterns. Molecular mechanisms for species differences in organic anion transporter 1, oat1. Defects in a new class of sulfateanion transporter link. The organic anion transporter 1 oat1 also known as solute carrier family 22 member 6 slc22a6 is a protein that in humans is encoded by the slc22a6 gene. 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. Slc26a1 sulfate anion transporter 1 homo sapiens human. Role of bloodbrain barrier organic anion transporter 3 oat3 in the efflux of indoxyl sulfate, a uremic toxin. Oct1 is primarily a hepatic uptake transporter, expressed on the sinusoidal membrane blood side of hepatocytes. Yohannes hagos, interaction of organic anion transporter 2 oat2 and sodium taurocholate cotransporting polypeptide ntcp with antineoplastic compounds, pharmacol res. Whereas in humans and the great apes, uric acid is the end product of purine degradation, in other mammals, it is further degraded into allantoin by uricase, an enzyme that is mostly found in the liver. Anti human organic anion transporter 1 oat1 polyclonal.
Organic anion transporters play an essential role in the distribution and excretion of numerous endogenous metabolic products and exogenous organic anions, including a host of widely prescribed drugs. Slco3a1 solute carrier organic anion transporter family member 3a1 heterocephalus glaber naked molerat. Endocrinology, volume 142, issue 10, 1 october 2001, pages 43394348. Human organic anion transporter 2 is distinct from organic. The anion exchanger sat1 sulfate anion transporter 1 slc26a1 is considered an important regulator of oxalate and sulfate homeostasis, but the mechanistic basis of these critical roles remain. The sulp family is a large and ubiquitous family of proteins derived from archaea, bacteria, fungi, plants and animals. Key role for the organic anion transporters, oat1 and oat3. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of. Organic anion transporter 1 an overview sciencedirect.
Naohiko anzai 1, yoshikatsu kanai 1, hitoshi endou 1 2 1 department of pharmacology and toxicology, kyorin university school of medicine, japan 2 fuji biomedix co. What does organic anion transporters, sodiumindependent mean. In biology, an ion transporter or ion pump is a transmembrane protein that moves ions across a biological membrane against their concentration gradient through active transport. Major role of organic anion transporter 3 in the transport. The slc26 gene family of anion transporters and channels. An enigmatic human solute carriers hong shen, yurong lai, and a.
Three splice variants that encode different isoforms have been identified. Canalicular multispecific organic anion transporter 1. Slco1c1 is thought to play a major role in regulating t4 flux in the brain. Pdzk1 and nherf1 regulate the function of human organic. The water molecule or sodium ion appears to stabilise the unwound. Thyroid hormone transport by the heterodimeric human system l. Slco3a1 solute carrier organic anion transporter family. Sulfate is involved in manymetabolic and cellular processes, and is essential for normal growth and development. Organic anion transporter 3 contributes to the regulation. Ion transporter definition of ion transporter by the. The prototypic organic anion transporter ligand bsp and the bile acid tc had little.
Transport properties of nonsteroidal antiinflammatory. Exhibits sodiumindependent sulfate anion transporter activity that may. This gene is primarily expressed in the liver, pancreas, and brain. Meaning of organic anion transporters, sodiumindependent.
Slco1a2 solute carrier organic anion transporter family. Organic anion transporter polypeptiderelated protein 2. We examined the substrate specificity of human organic anion transporter hoat 1 and hoat3 for various cephalosporin antibiotics, cephaloridine, cefdinir, cefotiam, ceftibuten, cefaclor, ceftizoxime, cefoselis and cefazolin by using hek293 cells stably transfected with hoat1 or hoat3 cdna hekhoat1, hekhoat3. Whereas cat1 functions to supply cationic amino acids for cellular. Targeted disruption of murine nas1 and sat1 leads to hyposulfatemia and hypersulfaturia. The current study aimed to establish a robust and a more complete human cell model suitable for screening of drugrelated interactions and. Targets 17enzymes 2carriers 1transporters 3biointeractions 25. Organic anion transporters oats play an essential role in the elimination of numerous endogenous and. Mediates sulfate transport with high affinity pubmed. Smt15 belongs to a previously uncharacterized subfamily of putative membranelocalized sulfateanion transporters that contain a sulfate transporter domain and are found in a widely distributed subset of eukaryotes and bacteria. Experiments with human embryonic kidney293 cells stably transfected with human oat1, oat2, or oat3 were performed to compare selected transport properties. Slc26asulp transporter domain ipr011547 oats are nonselective transporters prominent in the kidney, placenta and bloodbrain barrier.
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