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?
Materials. [3H]PAH (4.1 Ci/mmol), [3H]DHEAS (60 Ci/mmol), and [3H]ES (43.1 Ci/mmol) were purchased from PerkinElmer Life Science (Boston, MA). [14C]PCG (59 mCi/mmol) and [3H]2,4-D (20 Ci/mmol) were purchased from GE Healthcare Bio-Sciences (Waukesha, WI) and American Radiolabeled Chemicals (St. Louis, MO), respectively. Unlabeled PAH, DHEAS, ES, and 2,4-D were purchased from Sigma-Aldrich (St. Louis, MO), and unlabeled PCG and α-ketoglutarate (KG) were from Wako Pure Chemical Industries (Osaka, Japan). All other chemicals were of analytical grade and commercially available.. Preparation of Human Kidney Slices and Uptake of Organic Anions by Human Kidney Slices. This study protocol was approved by the Ethics Review Boards at both the Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan and Tokyo Womens Medical University, Tokyo, Japan. All participants provided written informed consent.. Intact renal cortical tissues were obtained from 42 surgically nephrectomized ...
anti-Solute Carrier Family 22 (Organic Anion Transporter), Member 8 (SLC22A8) antibody (Alexa Fluor 488) ABIN909357 from antibodies-online
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). ...
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
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A concordance as wide-reaching and readable as the translation its based on! This invaluable resource features a full English listing of every major word in the New Living Translation text along with the number of times it occurs. An introduction to the New Living Translation is included which offers the translation philosophy and methodology behind the version, names of scholars on the translation committee, text behind the NLT, translation issues, and an explanation of textual footnotes. Features: Full English concordance listings for every major word in the New Living TranslationsNumber of occurrences of each word listed Inclusion of many archaic terms and common renderings from other translations which are not found in the NLT NLT Comprehensive Concordance (9781414316994) by James A. Swanson
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.
Ezekiel 36 - I will cleanse you of your filthy behavior. I will give you good crops of grain, and I will send no more famines on the land.
Looking for online definition of solute carrier family 21 (organic anion transporter), member 9 in the Medical Dictionary? solute carrier family 21 (organic anion transporter), member 9 explanation free. What is solute carrier family 21 (organic anion transporter), member 9? Meaning of solute carrier family 21 (organic anion transporter), member 9 medical term. What does solute carrier family 21 (organic anion transporter), member 9 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 ...
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. ...
OATs belong to the solute carrier 22 transport protein superfamily, and they transport small, amphiphilic organic anions of diverse chemical structures. OAT1, the first OAT to be cloned, is strongly expressed in human kidney and localized at the basolateral membrane of the proximal tubule (Hosoyamada et al., 1999). OAT1 is known to play a central role in the renal uptake of a wide range of anionic xenobiotics, including endogenous metabolic waste products, environmental toxins, and numerous clinically important drugs (e.g., antibiotics, antivirals, anti-inflammatory drugs, diuretics, and anticancer agents) (Rizwan and Burckhardt, 2007; Burckhardt, 2012; Wang and Sweet, 2013b). In addition, OAT1 is involved in the development of nephrotoxicity of many anionic xenobiotics (Hagos and Wolff, 2010). Consequently, preloading of OAT1 inhibitors, including probenecid, betamiprone, and NSAIDs, has been reported to reduce OAT1-mediated drug nephrotoxicity (Tune et al., 1977; Hirouchi et al., 1994; Lacy et ...
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...
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 ...
The purpose of this study is to evaluate the effect of multiple-dose administration of probenecid on the pharmacokinetics of JNJ-63549109 and JNJ-64167896
SeaSpine (NSDQ:SPNE) said yesterday that it agreed to acquire Israeli firm NLT Spine in a deal that could wind up being worth $52.5 million.. Kfar Saba, Israel-based NLT makes a line of minimally invasive spinal implants for lumbar fusion procedures that are designed to expand after implantation. The deal with Carlsbad, Calif.-based SeaSpine, which spun out of Integra LifeSciences (NSDQ:IART last year, calls for an up-front cash payment of $1 million and up to $43 million more in contingent payments pegged to sales of the NLT products. SeaSpine has the option of making a 1-time payment of $18 million after the deal closes in lieu of any further contingent payouts.. The deal also includes a provision for $3.5 million worth of SeaSpine shares once the FDA clears NLTs Prow Fusion-L line and after Israeli officials sign off on the acquisition. Finally, theres $5 million on the line in cash or stock pegged to a quartet of commercialization milestones.. "This transaction strengthens our future ...
Thakkar N, Kim K, Jang ER, Han S, Kim K, Kim D, Merchant N, Lockhart AC, Lee W. A cancer-specific variant of the SLCO1B3 gene encodes a novel human organic anion transporting polypeptide 1B3 (OATP1B3) localized mainly in the cytoplasm of colon and pancreatic cancer cells. Mol Pharm. 2013;10(1):406-416. (PMID:23215050 ...
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The expression of the basolateral sodium-independent organic anion uptake system of the little skate (Raja erinacea) has been studied in Xenopus laevis oocytes. Injection of oocytes with skate liver poly(A)+ RNA resulted in the functional expression of chloride-dependent sulfobromophthalein (BSP) uptake and sodium-independent taurocholate uptake within 3-5 days. The expressed chloride-dependent BSP uptake activity exhibited saturation kinetics [apparent Michaelis constant (Km) 1.8 microM] and efficiently extracted BSP from its binding sites on bovine serum albumin. The chloride-sensitive portion of BSP uptake was inhibited by bilirubin (10 microM; 27%), 4,4-diisothiocyanostilbene-2,2-disulfonic acid (100 microM; 57%), bumetanide (100 microM; 48%), taurocholate (200 microM; 51%), and cholate (200 microM; 45%). Size fractionation of total skate liver mRNA revealed that a 1.8- to 2.9-kb size class mRNA was sufficient to express chloride-dependent BSP uptake and sodium-independent taurocholate ...
Uptake and efflux transporters determine plasma and tissue concentrations of a broad variety of drugs. They are localized in organs such as small intestine, liver, and kidney, which are critical for drug absorption and elimination. Moreover, they can be found in important blood-tissue barriers such as the blood-brain barrier. Inhibition or induction of drug transporters by coadministered drugs can alter pharmacokinetics and pharmacodynamics of the victim drugs. This review will summarize in particular clinically observed drug-drug interactions attributable to inhibition or induction of intestinal export transporters [P-glycoprotein (P-gp), breast cancer resistance protein (BCRP)], to inhibition of hepatic uptake transporters [organic anion transporting polypeptides (OATPs)], or to inhibition of transporter-mediated [organic anion transporters (OATs), organic cation transporter 2 (OCT2), multidrug and toxin extrusion proteins (MATEs), P-gp] renal secretion of xenobiotics ...
Figure 6. [3H]PAH efflux studies on X. laevis oocytes that were injected with water (mock) or hOAT4-cRNA. Three days after cRNA or water injection, 46 nl of a 200-μM [3H]PAH solution was injected into the oocytes, and efflux of [3H]PAH was measured, providing oocyte Ringers solution, chloride-free oocyte Ringers solution, and chloride-free oocyte Ringers solution plus 500 μM ES. The efflux was calculated as percentage of 3H content recovered in the supernatant compared with the sum of total radioactivity recovered in the medium and that remaining in the oocytes at the conclusion of a 30-min efflux period at room temperature, where hOAT4-expressing oocytes in oocyte Ringers solution were set to 100%, Data are means ± SEM or three independent experiments with five to seven oocytes each. **P , 0.01. ...
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
Correspondence to Dr. Frans G. M. Russel, Department of Pharmacology and Toxicology 233, Nijmegen Center for Molecular Life Sciences, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Phone: +31-24-3613691/3616892; Fax: +31-24-3614214; E-mail: F.Russel{at}farm.kun.nl ...
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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.
Complete information for SLCO2A1 gene (Protein Coding), Solute Carrier Organic Anion Transporter Family Member 2A1, 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
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.
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
You are their (our) glorious strength. It pleases You to make us strong. - (Psalm 89:17, NLT) ...because You are the splendor of their strength. By Your favor You make us strong. - (Psalm 89:17, CEB) God is gracious and kind, and He is pleased to provide the strength that we need to navigate…
We introduced several membrane-impermeant fluorescent dyes, including Lucifer Yellow, carboxyfluorescein, and fura-2, into the cytoplasmic matrix of J774 cells and thioglycollate-elicited mouse peritoneal macrophages by ATP permeabilization of the plasma membrane and observed the subsequent fate of these dyes. The dyes did not remain within the cytoplasmic matrix; instead they were sequestered within phase-lucent cytoplasmic vacuoles and released into the extracellular medium. We used Lucifer Yellow to study these processes further. In cells incubated at 37 degrees C, 87% of Lucifer Yellow was released from the cells within 30 min after dye loading. The dye that remained within the cells at this time was predominantly within cytoplasmic vacuoles. Lucifer yellow transport was temperature dependent and occurred against a concentration gradient; therefore it appeared to be an energy-requiring process. The fluorescent dyes used in these studies are all organic anions. We therefore examined the ...
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 ...
Chicken erythroblasts transformed with avian erythroblastosis virus or S13 virus provide suitable model systems with which to analyze the maturation of immature erythroblasts into erythrocytes. The transformed cells are blocked in differentiation at around the colony-forming unit-erythroid stage of development but can be induced to differentiate in vitro. Analysis of the expression and assembly of components of the membrane skeleton indicates that these cells simultaneously synthesize alpha-spectrin, beta-spectrin, ankyrin, and protein 4.1 at levels that are comparable to those of mature erythroblasts. However, they do not express any detectable amounts of anion transporter. The peripheral membrane skeleton components assemble transiently and are subsequently rapidly catabolized, resulting in 20-40-fold lower steady-state levels than are found in maturing erythrocytes. Upon spontaneous or chemically induced terminal differentiation of these cells expression of the anion transporter is initiated ...
The human solute carrier 26 (SLC26) family of anion transporters consists of ten members that are found in various organs in the body including the stomach, intestine, kidney, thyroid and ear where they transport anions including bicarbonate, chloride and sulfate, typically in an exchange mode. Mutations in these genes cause a plethora of diseases such as diastrophic dysplasia affecting sulfate uptake into chondrocytes (SLC26A2), congenital chloride-losing diarrhoea (SLC26A3) affecting chloride secretion in the intestine and Pendreds syndrome (SLC26A4) resulting in hearing loss. To understand how these mutations affect the structures of the SLC26 membrane proteins and their ability to function properly, 12 human disease-causing mutants from SLC26A2, SLC26A3 and SLC26A4 were introduced into the equivalent sites of the sulfate transporter anti-sigma factor antagonist (STAS) domain of a bacterial homologue SLC26 protein DauA (YchM). Biophysical analyses including size-exclusion chromatography, ...
Solute carrier family 22 member 8, or organic anion transporter 3 (OAT3), is a protein that in humans is encoded by the SLC22A8 gene. OAT3 is involved in the transport and excretion of organic ions some of which are drugs (e.g., penicillin G (benzylpenicillin), methotrexate (MTX), indomethacin (an NSAID), and ciprofloxacin (a fluoroquinolone antibiotic)) and some of which are pure toxicants. SLC22A8 (OAT3) is indirectly dependent on the inward sodium gradient, which is a driving force for reentry of dicarboxylates into the cytosol. Dicarboxylates, such as alpha-ketoglutarate generated within the cell, or recycled from the extracellular space, are used as exchange substrates to fuel the influx of organic anions against their concentration gradient. The encoded protein is an integral membrane protein and appears to be localized to the basolateral membrane of renal proximal tubule cells. GRCh38: Ensembl release 89: ENSG00000149452 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000063796 - ...
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] ...
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RI cGMP is an important modulating factor in P-N. Studies from our laboratory have suggested that RI cGMP acts through a mechanism that is independent of changes in renal hemodynamics and involves protein kinase G.3,15 In vitro studies in human RPT cells and in vivo studies in rats demonstrate that the production of cGMP by sGC and its export into the extracellular compartment through a PB-sensitive organic anion transporter are critical mechanisms for natriuretic responses to increased RPP.4,5,15. RIHP is another modulating factor of P-N. Increases in RPP lead to increases in RIHP, and the subsequent natriuresis is abolished by renal decapsulation.7 Increases in RIHP made by RI volume expansion lead to increases in natriuresis.6,16 Our studies address the relationship between these 2 important modulating factors of the P-N relationship.. The major findings of the present studies are described here. First, decreasing RIHP by renal decapsulation prevents the rise in RI cGMP levels and UNaV in ...
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Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties ...
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TY - JOUR. T1 - Action of EGF and PGE2 on basolateral organic anion uptake in rabbit proximal renal tubules and hOAT1 expressed in human kidney epithelial cells. AU - Sauvant, C.. AU - Hesse, D.. AU - Holzinger, H.. AU - Evans, K. K.. AU - Dantzler, William H. AU - Gekle, M.. PY - 2004/4. Y1 - 2004/4. N2 - We recently showed that, in a proximal tubule cell line (opossum kidney cells), epithelial growth factor (EGF) stimulates basolateral organic anion transport (OAT) via ERK1/2, arachidonic acid, phospholipase A2, and generation of prostaglandins. PGE2 binds the prostanoid receptor and, thus, activates adenylate cyclase and PKA, which stimulate basolateral organic anion uptake. In the present study, we investigated whether this regulatory cascade is also true 1) for ex vivo conditions in isolated renal proximal (S2) tubules from rabbit and 2) in a human renal epithelial cell line stably expressing human OAT1 (IHKE-hOAT1). EGF activated ERK1/2 in S2 tubules and IHKE-hOAT1, and, in both cases, ...
Purpose. Biliary organic anion excretion is mediated by an ATP-dependent primary active transporter, a so-called canalicular multispecific organic anion transporter (cMOAT). As there appear to be many canalicular organic anion transports, we examined the effects of various organic anions and bile acid conjugates on the biliary excretion of pravastatin in rats. Methods. [l4C]pravastatin was intravenously injected into rats with bile drainage in the presence and absence of the continuous infusion of organic anions and bile acids, and radioactivity of its biliary excretion was studied. Results. Biliary excretion of [14C]pravastatin was markedly inhibited by sulfobromophthalein-glutathione, taurolithocholate-3-sulfate, ursodeoxycholate-3,7-sulfate, and ursodeoxycholate-3-O-glucuronide. In contrast, dibromosulfophthalein only slightly inhibited biliary pravastatin excretion, and cefpiramide did not affect biliary pravastatin excretion. Conclusions. These findings further support the multiplicity of
Entecavir (ETV) is one of the most potent agents for the treatment of the hepatitis B viral infection. The drug is principally eliminated by the kidney. The goal of this study was to investigate the potential of ETV to interact in vitro with the renal SLC transporters hOAT1, hOCT2, hCNT2 and hCNT3. Potential drug-drug interactions of ETV at the renal transporters with antiviral drugs known to be excreted by the kidney (adefovir, tenofovir, cidofovir) as well as transporter-dependent cytotoxicity were also examined. Interactions with the selected transporters along with cytotoxicity were studied in several transiently-transfected cellular models using specific substrates and inhibitors. ETV was found to be both a substrate and inhibitor of hOAT1 (IC50 = 175.3 µM), hCNT2 (IC50 = 241.9 µM) and hCNT3 (IC50 = 278.4 µM) transporters, although it interacted with the transporters with relatively low affinities. ETV inhibited the cellular uptake of adefovir, tenofovir and cidofovir by hOAT1; however,
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. ...
TY - JOUR. T1 - Capsaicinoids regulate airway anion transporters through rho kinase- and cyclic AMP-dependent mechanisms. AU - Hibino, Yoshitaka. AU - Morise, Masahiro. AU - Ito, Yasushi. AU - Mizutani, Takefumi. AU - Matsuno, Tadakatsu. AU - Ito, Satoru. AU - Hashimoto, Naozumi. AU - Sato, Mitsuo. AU - Kondo, Masashi. AU - Imaizumi, Kazuyoshi. AU - Hasegawa, Yoshinori. PY - 2011/10/1. Y1 - 2011/10/1. N2 - To investigate the effects of capsaicinoids on airway anion transporters, we recorded and analyzed transepithelial currents in human airway epithelial Calu-3 cells. Application of capsaicin (100 μM) attenuated vectorial anion transport, estimated as short-circuit currents (I SC), before and after stimulation by forskolin (10 μM) with concomitant reduction of cytosolic cyclic AMP (cAMP) levels. The capsaicin-induced inhibition of I SC was also observed in the response to 8-bromo-cAMP (1 mM, a cell-permeable cAMP analog) and 3-isobutyl-1-methylxanthine (1 mM, an inhibitor of ...