This project is supported by the Canadian Institutes of Health Research (award #111062), Alberta Innovates - Health Solutions, and by The Metabolomics Innovation Centre (TMIC), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta, Genome British Columbia, and Genome Canada, a not-for-profit organization that is leading Canadas national genomics strategy with funding from the federal government. Maintenance, support, and commercial licensing is provided by OMx Personal Health Analytics, Inc. Designed by Educe Design & Innovation Inc. ...
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Solute carrier organic anion transporter family member 1A2 is a protein that in humans is encoded by the SLCO1A2 gene.[1][2] This gene encodes a sodium-independent transporter which mediates cellular uptake of organic ions in the liver. Its substrates include bile acids, bromosulphophthalein, and some steroidal compounds. The protein is a member of the SLC21A family of solute carriers. Alternate splicing of this gene results in three transcript variants encoding two different isoforms.[2] ...
Complete information for SLCO1B3 gene (Protein Coding), Solute Carrier Organic Anion Transporter Family Member 1B3, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for SLCO1A2 gene (Protein Coding), Solute Carrier Organic Anion Transporter Family Member 1A2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Gene target information for Slco1a1 - solute carrier organic anion transporter family, member 1a1 (house mouse). Find diseases associated with this biological target and compounds tested against it in bioassay experiments.
SLCO1A2 antibody (solute carrier organic anion transporter family, member 1A2) for ELISA, WB. Anti-SLCO1A2 pAb (GTX87607) is tested in Human samples. 100% Ab-Assurance.
Selected publications:. Kanai,N Lu,R Satriano,J Bao,Y Wolkoff,AW Schuster,VL. Identification and characterization of a prostaglandin transporter. Science 268: 866-869, 1995.. Itoh,S Lu,R Bao,Y Morrow,JD Roberts,LJ Schuster,VL. Structural determinants of substrates for the prostaglandin transporter "PGT". Mol Pharm 50: 736-742, 1996.. Lu,R Kanai,N Bao,Y Schuster,VL. Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA "hPGT". J Clin Invest 98: 1142-1149, 1996.. Schuster,VL Lu,R Coca-Prados,M. Identification and characterization of a prostaglandin transporter widely-expressed in ocular and other secretory epithelia. Survey Ophthalmol 41: S41-S45, 1997.. Schuster,VL. Molecular mechanisms of prostaglandin transport. Ann Rev Physiol 60: 221-242, 1998.. Chan,B Satriano,JA Pucci,M Schuster,VL. Mechanism of PGE2 transport across the plasma membrane of HeLa cells and Xenopus oocytes expressing the prostaglandin transporter "PGT". J Biol Chem 273: 6689-6697, ...
Interindividual variability in protein expression of organic anion-transporting polypeptides (OATPs) OATP1B1, OATP1B3, OATP2B1, and multidrug resistance-linked P-glycoprotein (P-gp) or ABCB1 was quantified in frozen human livers (n = 64) and cryopreserved human hepatocytes (n = 12) by a validated liquid chromatography tandem mass spectroscopy (LC-MS/MS) method. Membrane isolation, sample workup, and LC-MS/MS analyses were as described before by our laboratory. Briefly, total native membrane proteins, isolated from the liver tissue and cryopreserved hepatocytes, were trypsin digested and quantified by LC-MS/MS using signature peptide(s) unique to each transporter. The mean ± S.D. (maximum/minimum range in parentheses) protein expression (fmol/µg of membrane protein) in human liver tissue was OATP1B1- 2.0 ± 0.9 (7), OATP1B3- 1.1 ± 0.5 (8), OATP2B1- 1 1.7 ± 0.6 (5), and P-gp- 0.4 ± 0.2 (8). Transporter expression in the liver tissue was comparable to that in the cryopreserved hepatocytes. ...
In the present study, we found that the C-1 carboxylic acid group was essential for optimal substrate binding to the FP receptor. Replacement of the carboxylic acid group by larger moieties with a similar pK a, such as acylsulfonamide and tetrazole, substantially decreased binding affinity. The prostaglandin transporter PGT, on the other hand, recognized a fairly wide range of anionic substrates at C-1. In contrast, insertion of cyclic substituents in the omega chain increased binding to the FP receptor but reduced affinity for PGT, and substitution for the 15-hydroxyl group produced only a modest reduction in FP receptor binding but eliminated binding by PGT.. Prostaglandins and thromboxanes bind to a number of structurally diverse molecules, such as their cell-surface receptors (EP, FP, IP, DP, and TP) (Breyer et al., 1996a), the prostaglandin transporter PGT (Itoh et al., 1996), peroxisome proliferator-activated receptors α and γ (Forman et al., 1995; Kliewer et al., 1995), and ...
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We characterized the interactions of various compounds with OAT-K1 and OAT-K2, kidney-specific organic anion transporters. By using Madin-Darby canine kidney cells stably transfected with OAT-K1 or OAT-K2 cDNA, the antitumor drug methotrexate, the mycotoxin ochratoxin A, endogenous organic anions (thyroid hormones, taurocholic acid, and conjugated steroids), and the antiretroviral drug zidovudine were shown to be substrates for these transporters. Although the apparent Michaelis constant (Km) values of methotrexate for OAT-K1 and OAT-K2 were 2.1 and 1.8 μM, respectively, 2.5 mM methotrexate inhibited only 20% of the 125I-thyroid hormones uptake via these transporters. In addition, 100 μM methotrexate did not have any effect on [3H]zidovudine uptake via OAT-K1 or OAT-K2. Similarly, several substrates caused little or no mutual inhibition at concentrations much higher than theirKm values for these transporters. Moreover, intracellular methotrexate trans-stimulated the OAT-K1- and OAT-K2-mediated ...
With efforts to reduce cytochrome P450-mediated clearance (CL) during the early stages of drug discovery, transporter-mediated CL mechanisms are becoming more prevalent. However, the prediction of plasma concentration-time profiles for such compounds using physiologically based pharmacokinetic (PBPK) modeling is far less established in comparison with that for compounds with passively mediated pharmacokinetics (PK). In this study, we have assessed the predictability of human PK for seven organic anion-transporting polypeptide (OATP) substrates (pravastatin, cerivastatin, bosentan, fluvastatin, rosuvastatin, valsartan, and repaglinide) for which clinical intravenous data were available. In vitro data generated from the sandwich culture human hepatocyte system were simultaneously fit to estimate parameters describing both uptake and biliary efflux. Use of scaled active uptake, passive distribution, and biliary efflux parameters as inputs into a PBPK model resulted in the overprediction of exposure ...
3. Bodeman, C.E.; Dzierlenga, A.L.; Tally, C.M.; Mulligan, R.M.; Lake, A.D.; Cherrington, N.J.; McKarns, S.C. "Differential Regulation of Hepatic Organic cation Transporter 1. Organic Anion-Transporting Polypeptide 1a4, Bile-Salt Export Pump, and Multidrug Resistance-Associated Protein 2.Transporter Expression in Lymphocyte-Deficient Mice Associates with Interleukin-6 Production." J Pharmacol Exp Ther., 2013, 347, 136-144 ...
Beyond their roles in generating nerve impulses, ion channels are important for many facets of cell biology, including swelling and osmotic stress responses. Sabirov and colleagues now report that the prostaglandin transporter SLCO2A1 is a central component of the ubiquitous Maxi‐Cl anion channel. These findings add to a growing number of transporters displaying ion channel activity and not only provide a molecular handle for future Maxi‐Cl physiological and biophysical studies, but also underscore general questions about the principles that underlie such transporter/channel dual‐use behavior.. See also: RZ Sabirov et al (November 2017) ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
In this study, we characterized the transport function and transcriptional regulation of the OATP2B1 1e variant. The SLCO2B1 1e variant encoding OATP2B1-Short was cloned from a human liver cDNA library. Heterologous expression of OATP2B1-Short (1e) in HeLa cells resulted in cell surface expression and functional transport activity. We found no pronounced differences in transport activity between the OATP2B1-FL and OATP2B1-Short proteins for two typical OATP substrates: rosuvastatin and estrone 3-sulfate. However, we did see a significant increase in rosuvastatin uptake by OATP2B1-Short, but not for OATP2B1-FL at low pH. Reporter assays, siRNA knockdown, and ChIP revealed a functional HNF4α binding motif in the proximal region of the SLCO2B1 1e promoter.. The expression of the alternative OATP2B1 variants in intestine and kidney was previously reported (Pomari et al., 2009). We confirm that the OATP2B1 exon 1b transcription variant has a broad expression pattern consistent with previous reports ...
The second in a pair of articles on drug transporters, this article focuses on uptake transporters that actively pump drugs into cells.
Looking for online definition of Organic anion-transporting polypeptide 14 in the Medical Dictionary? Organic anion-transporting polypeptide 14 explanation free. What is Organic anion-transporting polypeptide 14? Meaning of Organic anion-transporting polypeptide 14 medical term. What does Organic anion-transporting polypeptide 14 mean?
Solute carrier organic anion transporter family member 2A1 (OATP2A1, encoded by the SLCO2A1 gene), which was initially identified as prostaglandin transporter (PGT), is expressed ubiquitously in tissues and mediates the distribution of prostanoids, such as PGE, PGF, PGDand TxB. It is well known to play a key role in the metabolic clearance of prostaglandins, which are taken up into the cell by OATP2A1 and then oxidatively inactivated by 15-ketoprostaglandin dehydrogenase (encoded by HPGD); indeed, OATP2A1-mediated uptake is the rate-limiting step of PGEcatabolism. Consequently, since OATP2A1 activity is required for termination of prostaglandin signaling via prostanoid receptors, its inhibition can enhance such signaling. Read More ...
Junji Umeno, Tadakazu Hisamatsu, Motohiro Esaki, Atsushi Hirano, Takayuki Matsumoto, Kitazono T, A Hereditary Enteropathy Caused by Mutations in the SLCO2A1 Gene, Encoding a Prostaglandin Transporter., e1005581, 2015.11, Previously, we proposed a rare autosomal recessive inherited enteropathy characterized by persistent blood and protein loss from the small intestine as chronic nonspecific multiple ulcers of the small intestine (CNSU). By whole-exome sequencing in five Japanese patients with CNSU and one unaffected individual, we found four candidate mutations in the SLCO2A1 gene, encoding a prostaglandin transporter. The pathogenicity of the mutations was supported by segregation analysis and genotyping data in controls. By Sanger sequencing of the coding regions, 11 of 12 other CNSU patients and 2 of 603 patients with a diagnosis of Crohns disease were found to have homozygous or compound heterozygous SLCO2A1 mutations. In total, we identified recessive SLCO2A1 mutations located at seven ...
Results Compared with NL, hepatic mRNA and protein levels of FAT/CD36 were significantly higher in patients with NAS (median fold increase 0.84 (range 0.15-1.61) and 0.66 (range 0.33-1.06), respectively); NASH (0.91 (0.22-1.81) and 0.81 (0.38-0.92), respectively); HCV G1 without steatosis (0.30 (0.17-1.59) and 0.33 (0.29-0.52), respectively); and HCV G1 with steatosis (0.85 (0.15-1.98) and 0.87 (0.52-1.26), respectively). In contrast to NL, FAT/CD36 was predominantly located at the plasma membrane of hepatocytes in patients with NAFLD and HCV G1 with steatosis. A significant correlation was observed between hepatic FAT/CD36 expression index and plasma insulin levels, insulin resistance (HOMA-IR) and histological grade of steatosis in patients with NASH (r=0.663, r=0.735 and r=0.711, respectively) and those with HCV G1 with steatosis (r=0.723, r=0.769 and r=0.648, respectively). ...
BACKGROUND: Lowering low-density lipoprotein cholesterol with statin therapy results in substantial reductions in cardiovascular events, and larger reductions in cholesterol may produce larger benefits. In rare cases, myopathy occurs in association with statin therapy, especially when the statins are administered at higher doses and with certain other medications. METHODS: We carried out a genomewide association study using approximately 300,000 markers (and additional fine-mapping) in 85 subjects with definite or incipient myopathy and 90 controls, all of whom were taking 80 mg of simvastatin daily as part of a trial involving 12,000 participants. Replication was tested in a trial of 40 mg of simvastatin daily involving 20,000 participants. RESULTS: The genomewide scan yielded a single strong association of myopathy with the rs4363657 single-nucleotide polymorphism (SNP) located within SLCO1B1 on chromosome 12 (P=4x10(-9)). SLCO1B1 encodes the organic anion-transporting polypeptide OATP1B1, which has
anti-Solute Carrier Family 22 (Organic Anion Transporter), Member 8 (SLC22A8) antibody (Alexa Fluor 488) ABIN909357 from antibodies-online
Affiliation:The University of Tokyo,Faculty of Medicine,Research Associate,医学部附属病院,助手, Research Field:応用薬理学・医療系薬学,General pharmacology,Kidney internal medicine,Pediatrics,Pediatrics, Keywords:エストロン硫酸,Na^+,近位尿細管性アシドーシス,パラアミノ馬尿酸,rBAT,オクラトキシンA,organic anion transporter2,organic anion transporter3,organic anion transporter1,BAT1, # of Research Projects:8, # of Research Products:9
The mechanism of release and the role of l-aspartate as a central neurotransmitter are controversial. A vesicular release mechanism for l-aspartate has been difficult to prove, as no vesicular l-aspartate transporter was identified until it was found that sialin could transport l-aspartate and l-glutamate when reconstituted into liposomes. We sought to clarify the release mechanism of l-aspartate and the role of sialin in this process by combining l-aspartate uptake studies in isolated synaptic vesicles with immunocyotchemical investigations of hippocampal slices. We found that radiolabeled l-aspartate was taken up into synaptic vesicles. The vesicular l-aspartate uptake, relative to the l-glutamate uptake, was twice as high in the hippocampus as in the whole brain, the striatum, and the entorhinal and frontal cortices and was not inhibited by l-glutamate. We further show that sialin is not essential for exocytosis of l-aspartate, as there was no difference in ATP-dependent l-aspartate uptake in ...
TY - JOUR. T1 - Localization of organic anion transporting polypeptide 3 (oatp3) in mouse brain parenchymal and capillary endothelial cells. AU - Ohtsuki, Sumio. AU - Takizawa, Takuya. AU - Takanaga, Hitomi. AU - Hori, Satoko. AU - Hosoya, Ken Ichi. AU - Terasaki, Tetsuya. PY - 2004/8/1. Y1 - 2004/8/1. N2 - Organic anion transporting polypeptide 3 (oatp3) transports various CNS-acting endogenous compounds, including thyroid hormones and prostaglandin E2, between extra- and intracellular spaces, suggesting a possible role in CNS function. The purpose of this study was to clarify the expression and localization of oatp3 in the mouse brain. RT-PCR analysis revealed that oatp3 mRNA is expressed in brain capillary-rich fraction, conditionally immortalized brain capillary endothelial cells, choroid plexus, brain and lung, but not in liver or kidney, where oatp1, 2 and 5 mRNAs were detected. Immunohistochemical analysis with anti-oatp3 antibody suggests that oatp3 protein is localized at the ...
BioAssay record AID 682056 submitted by ChEMBL: TP_TRANSPORTER: uptake (pH 5.0) of Estrone-3-sulfate at a concentration of 5.43 nM in OATP-B-expressing HEK293 cells.
Aus pharmakologischer Sicht sind unter den Aufnahmetransportern Vertreter der organic anion transporting polypeptide-Familie (OATPs) von besonderem Interesse. Transporter dieser Familie besitzen nicht nur ein breites Substratspektrum endogener und exogener Substanzen, sondern sind auch in zahlreichen Geweben exprimiert. Gut untersucht ist dabei vor allem die Leber mit den vorwiegend hepatisch exprimierten Vertretern OATP1B1 und OATP1B3, während zur Expression und Funktion der OATPs in weiteren pharmakologischen Zielstrukturen, wie beispielsweise den Blutzellen oder auch der Blut-Hirn-Schranke, weit weniger bekannt ist. Ziel dieser Arbeit war es daher, ausgewählte OATP-Transporter hinsichtlich ihrer Expression, ihrem Interaktionspotential und der Funktion in der Blut-Hirn-Schranke und zwei Blutzellpopulationen zu charakterisieren. Dabei konnte zunächst die Expression des OATP2B1 und OATP1A2 in der Blut-Hirn-Schranke bestätigt und deren funktionelle Interaktion mit ausgewählten Dopaminrezeptor
Ramuan tradisional untuk obat asam urat adalah obat yang banyak dicari oleh wanita, dan pria yang berumur di atas 30 tahun, karena banyak yang terkena penyakit asam urat. bahkan sekarang di bawah umur 30 tahun sudah terkena asam urat akut. jika penyakit sudah parah akan mengakibatkan persendian tidak bisa bergerak. tetapi anda tidak usah khawatir, karena sekarang sudah muncul obat untuk asam urat herbal tradisional berkhasiat tinggi. obat asam urat yang alami ampuh dari dulu tradisional ini adalah salah satu obat herbal asam urat dan kolesterol menahun tradisional berkhasiat tinggi, dan obat asam urat herbal tradisional terbaik alami ampuh dari dulu. tidak hanya bisa dijadikan untuk obat asam urat dan testimoni penderita asam urat, tetapi bisa juga mengobati kolesterol tinggi ...
Ramuan tradisional untuk obat asam urat adalah obat yang banyak dicari oleh wanita, dan pria yang berumur di atas 30 tahun, karena banyak yang terkena penyakit asam urat. bahkan sekarang di bawah umur 30 tahun sudah terkena asam urat akut. jika penyakit sudah parah akan mengakibatkan persendian tidak bisa bergerak. tetapi anda tidak usah khawatir, karena sekarang sudah muncul obat untuk asam urat herbal tradisional berkhasiat tinggi. obat asam urat yang alami ampuh dari dulu tradisional ini adalah salah satu obat herbal asam urat dan kolesterol menahun tradisional berkhasiat tinggi, dan obat asam urat herbal tradisional terbaik alami ampuh dari dulu. tidak hanya bisa dijadikan untuk obat asam urat dan testimoni penderita asam urat, tetapi bisa juga mengobati kolesterol tinggi ...
Ramuan tradisional untuk obat asam urat adalah obat yang banyak dicari oleh wanita, dan pria yang berumur di atas 30 tahun, karena banyak yang terkena penyakit asam urat. bahkan sekarang di bawah umur 30 tahun sudah terkena asam urat akut. jika penyakit sudah parah akan mengakibatkan persendian tidak bisa bergerak. tetapi anda tidak usah khawatir, karena sekarang sudah muncul obat untuk asam urat herbal tradisional berkhasiat tinggi. obat asam urat yang alami ampuh dari dulu tradisional ini adalah salah satu obat herbal asam urat dan kolesterol menahun tradisional berkhasiat tinggi, dan obat asam urat herbal tradisional terbaik alami ampuh dari dulu. tidak hanya bisa dijadikan untuk obat asam urat dan testimoni penderita asam urat, tetapi bisa juga mengobati kolesterol tinggi ...
Ramuan tradisional untuk obat asam urat adalah obat yang banyak dicari oleh wanita, dan pria yang berumur di atas 30 tahun, karena banyak yang terkena penyakit asam urat. bahkan sekarang di bawah umur 30 tahun sudah terkena asam urat akut. jika penyakit sudah parah akan mengakibatkan persendian tidak bisa bergerak. tetapi anda tidak usah khawatir, karena sekarang sudah muncul obat untuk asam urat herbal tradisional berkhasiat tinggi. obat asam urat yang alami ampuh dari dulu tradisional ini adalah salah satu obat herbal asam urat dan kolesterol menahun tradisional berkhasiat tinggi, dan obat asam urat herbal tradisional terbaik alami ampuh dari dulu. tidak hanya bisa dijadikan untuk obat asam urat dan testimoni penderita asam urat, tetapi bisa juga mengobati kolesterol tinggi ...
Ramuan tradisional untuk obat asam urat adalah obat yang banyak dicari oleh wanita, dan pria yang berumur di atas 30 tahun, karena banyak yang terkena penyakit asam urat. bahkan sekarang di bawah umur 30 tahun sudah terkena asam urat akut. jika penyakit sudah parah akan mengakibatkan persendian tidak bisa bergerak. tetapi anda tidak usah khawatir, karena sekarang sudah muncul obat untuk asam urat herbal tradisional berkhasiat tinggi. obat asam urat yang alami ampuh dari dulu tradisional ini adalah salah satu obat herbal asam urat dan kolesterol menahun tradisional berkhasiat tinggi, dan obat asam urat herbal tradisional terbaik alami ampuh dari dulu. tidak hanya bisa dijadikan untuk obat asam urat dan testimoni penderita asam urat, tetapi bisa juga mengobati kolesterol tinggi ...
Mouse polyclonal antibody raised against a full-length human SLCO3A1 protein. SLCO3A1 (ABM82880.1, 1 a.a. ~ 692 a.a) full-length human protein. (H00028232-B01P) - Products - Abnova
An economic simulation where you build up production chains as effectively as possible on a large scale terrain. You can choose from a large variety of wares and buildings to build up your production chain and use up to 4 types of transportation ...
S, the measurement of overall level of carbonyls of plasma proteins may be used as a surrogate marker of oxidative modification of VWF, as shown in the present
Hardly any effect .The absence of an association of buy GW0742 survival together with the far more frequent variants (like CYP2D6*4) prompted these
Herbal Online , Grosir Herbal Cirebon , Jual obat herbal , Madu , Habbatussauda , Minyak zaitun , Herbal Asam Urat , Obat Herbal ...
Looking for online definition of Sodium-independent organic anion transporter E in the Medical Dictionary? Sodium-independent organic anion transporter E explanation free. What is Sodium-independent organic anion transporter E? Meaning of Sodium-independent organic anion transporter E medical term. What does Sodium-independent organic anion transporter E mean?
TY - JOUR. T1 - Functional analysis of rat renal organic anion transporter OAT-K1. T2 - Bidirectional methotrexate transport in apical membrane. AU - Masuda, Satohiro. AU - Takeuchi, Ayako. AU - Saito, Hideyuki. AU - Hashimoto, Yukiya. AU - Inui, Ken Ichi. PY - 1999/10/1. Y1 - 1999/10/1. N2 - Renal organic anion transporter OAT-K1 was stably transfected in MDCK cells and examined for its transport characteristics and membrane localization. OAT-K1 mediated both uptake and efflux of methotrexate in the apical membranes. Immunoblotting showed that the apparent molecular mass of the expressed OAT-K1 was 50 kDa, which was comparable to that found in the rat renal brush-border membranes. The OAT-K1-mediated methotrexate transport was significantly inhibited in the presence of several organic anions such as folate and sulfobromophthalein. These findings suggest that OAT-K1 mediates bidirectional methotrexate transport across the apical membranes, and may be involved in the renal handling of ...
Urate transport in the kidney proximal tubule is a bidirectional process. Although the urate reabsorption pathway has been elucidated recently, there is little knowledge about the excretory route. The basolateral organic anion transporters OAT1 and OAT3 presumably mediate uptake from blood into the cell, but for apical export from the cell into urine no candidate transporter has been identified. In this study, we show that the apical organic anion transporter MRP4 mediates ATP-dependent urate transport in isolated membrane vesicles and exports urate from transfected cells. Furthermore, the complex interaction pattern of urate with the MRP4 substrates MTX, cAMP, and cGMP indicates that MRP4 is an organic anion transporter with multiple allosteric binding sites.. Isolated apical and basolateral membrane vesicles from kidney proximal tubule have been used widely to study organic anion transport mechanisms, mainly using PAH or urate as a substrate (31). In contrast to basolateral membrane vesicles, ...
Organic anions of diverse chemical structures are secreted in renal proximal tubules. The first step in secretion, uptake of organic anions across the basolateral membrane of tubule cells, is...
[18F]Fluciclovine (trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid; anti-[18F]FACBC), a positron emission tomography tracer used for the diagnosis of recurrent prostate cancer, is transported via amino acid transporters (AATs) with high affinity (Km: 97-230 μM). However, the mechanism underlying urinary excretion is unknown. In this study, we investigated the involvement of AATs and drug transporters in renal [18F]fluciclovine reuptake. [14C]Fluciclovine (trans-1-amino-3-fluoro[1-14C]cyclobutanecarboxylic acid) was used because of its long half-life. The involvement of AATs in [14C]fluciclovine transport was measured by apical-to-basal transport using an LLC-PK1 monolayer as model for renal proximal tubules. The contribution of drug transporters herein was assessed using vesicles/cells expressing the drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug resistance-associated protein 4 (MRP4), organic anion transporter 1 (OAT1), organic anion transporter 3
OAT1 is a multispecific organic anion transporter exclusively located on the basolateral membrane of the middle proximal tubule, S2 segment (Tojo et al., 1999). PAH is a high-affinity substrate of OAT1 (Km = 14.3 μM), and OAT1-mediated PAH transport was inhibited by a variety of anionic drugs (Sekine et al., 1997). OAT1 is an organic anion/dicarboxylate exchanger; preloaded glutarate trans-stimulates the uptake of PAH via OAT1 (Sekine et al., 1997). From these findings, we inferred that OAT1 is the major renal organic anion transporter at the basolateral membrane of the proximal tubule. However, the contribution of OAT1 in the renal excretion of organic anions remains to be elucidated. In fact, we have already identified several isoforms of OAT1 (Sekine et al., 1998), one of which shows higher affinity to PCG.. This study demonstrated the inhibition of PAH transport via OAT1 by all the penicillins and cephalosporins tested and OAT1-mediated transport of [3H]PCG and [14C]cephaloridine (Fig. 3). ...
Chemical synapses are the principal locations where signals are transmitted between neurons. The transmission of this chemical signal is largely influenced by the action of neurotransmitter transporters which contribute to synaptic transmission by removing neurotransmitters from the synaptic cleft and thus terminating the synaptic signal. Abnormal activities of neurotransmitter transporters are associated with a variety of brain disorders. Therefore, drugs targeting neurotransmitter transporters play an important role in treating these diseases.; Since only the neurotransmitter transporters present on the plasma membrane are able to take up synaptically localized transmitters, it is critical to maintain a proper number of surface transporters. Recent advances in transporter biochemistry and molecular biology have provided substantial insights into transporter structure and function, intracellular transporter trafficking, and the association of transporters with other cellular proteins. All of ...
Chemical synapses are the principal locations where signals are transmitted between neurons. The transmission of this chemical signal is largely influenced by the action of neurotransmitter transporters which contribute to synaptic transmission by removing neurotransmitters from the synaptic cleft and thus terminating the synaptic signal. Abnormal activities of neurotransmitter transporters are associated with a variety of brain disorders. Therefore, drugs targeting neurotransmitter transporters play an important role in treating these diseases.; Since only the neurotransmitter transporters present on the plasma membrane are able to take up synaptically localized transmitters, it is critical to maintain a proper number of surface transporters. Recent advances in transporter biochemistry and molecular biology have provided substantial insights into transporter structure and function, intracellular transporter trafficking, and the association of transporters with other cellular proteins. All of ...
Thiazide diuretics are among the most widely used treatments for hypertension, but thiazide-induced hyponatremia (TIH), a clinically significant adverse effect, is poorly understood. Here, we have studied the phenotypic and genetic characteristics of patients hospitalized with TIH. In a cohort of 109 TIH patients, those with severe TIH displayed an extended phenotype of intravascular volume expansion, increased free water reabsorption, urinary prostaglandin E2 excretion, and reduced excretion of serum chloride, magnesium, zinc, and antidiuretic hormone. GWAS in a separate cohort of 48 TIH patients and 2,922 controls from the 1958 British birth cohort identified an additional 14 regions associated with TIH. We identified a suggestive association with a variant in SLCO2A1, which encodes a prostaglandin transporter in the distal nephron. Resequencing of SLCO2A1 revealed a nonsynonymous variant, rs34550074 (p.A396T), and association with this SNP was replicated in a second cohort of TIH cases. TIH ...
The OAT (organic anion transporter) family mediates the absorption, distribution and excretion of a diverse array of environmental toxins and clinically important drugs. OAT dysfunction significantly contributes to renal, hepatic, neurological and fetal toxicity and disease. As a first step to establish the topological model of hOAT1 (human OAT1), we investigated the external loops and the cellular orientation of the N- and the C-termini of this transporter. Combined approaches of immunofluorescence studies and site-directed chemical labelling were used for such purpose. Immunofluorescence microscopy of Myc-tagged hOAT1 expressed in cultured cells identified that both the N- and the C-termini of the transporter were located in the cytoplasm. Replacement of Lys59 in the predicted extracellular loop I with arginine resulted in a mutant (K59R), which was largely inaccessible for labelling by membrane-impermeable NHS (N-hydroxysuccinimido)-SS (dithio)-biotin present in the extracellular medium. This ...