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Anion Transporters (anion + transporter)

Distribution by Scientific Domains
Medical Sciences43%
Chemistry37%
Life Sciences18%

Kinds of Anion Transporters

  • organic anion transporter
    		•

    Selected Abstracts

    Structure, function, and regulation of renal organic anion transporters

    MEDICINAL RESEARCH REVIEWS, Issue 6 2002
    Guofeng You
    Abstract Renal elimination of anionic drugs, xenobiotics, and toxins is necessary for the survival of mammalian species. This process is mediated by vectorial transport from blood to urine through the cooperative functions of specific transporters in the basolateral and apical membranes of the proximal tubule epithelium. The first step of this process is the extraction of organic anions from the peritubular blood plasma into proximal tubule cells largely through the organic anion transporter (OAT) pathway. Therefore, the OAT pathway is one of the major sites for body drug clearance/detoxification. As a result, it is also the site for drug,drug interaction and drug-induced nephrotoxicity. To maximize therapeutic efficacy and minimize toxicity, the structure-function relationships of OATs and their regulation must be defined. The recent cloning and identification of OATs have paved the way for such investigations. This review summarizes the available data on the general properties of OATs, focusing in particular on the recent progress made from the author's laboratory as well as from other's, on the molecular characterization of the structure-function relationships of OATs and their regulatory mechanisms. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 6, 602,616, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10019 [source]

    Prevalence of risk factors for statin-induced myopathy in rheumatoid arthritis patients

    MUSCULOSKELETAL CARE, Issue 1 2010
    Tracey E. Toms MBChB MRCP
    Abstract Objectives:,Statins are widely prescribed in patients with rheumatoid arthritis (RA). Although statins offer overwhelming cardiovascular benefits, their use can be associated with the development of a statin-induced myopathy. Several factors increase the risk of developing statin-induced myopathy, including the single nucleotide polymorphism (SNP) rs4149056, located within the gene encoding solute carrier organic anion transporter (SLCO1B1). We aimed to identify the frequency of risk factors for statin-induced myopathy and establish whether the rs4149056 genotype is more prevalent in RA. Methods:,A total of 396 RA patients and 438 non-RA controls were studied. DNA samples were obtained from all patients. The SNP rs4149056 was identified using real-time polymerase chain reaction and melting curve analysis. Genotypic and allelic frequencies were calculated using the chi-squared test. Results:,Almost 80% of RA patients had one or more risk factor (range 1,5) for the development of statin-induced myopathy. Of the 74 RA patients treated with statins, 90% had one or more (range 1,4) risk factors. No differences in genotype or allelic frequencies were observed between RA patients and controls. Conclusions:,RA patients harbour multiple risk factors for statin-induced myopathy. However, the frequency of the rs4149056 genotypes does not differ according to the presence of RA. Despite this, no cases of statin-induced myopathy were observed in this cohort over a period of four years of follow-up. Thus, we conclude that statin use among RA patients is probably safe, but large-scale prospective studies are needed to confirm this. In the meantime, it may be good practice systematically to consider and record myopathy risk factors in these patients. Copyright © 2009 John Wiley & Sons, Ltd [source]

    A common ABCC2 promoter polymorphism is not a determinant of the risk of spina bifida ,

    BIRTH DEFECTS RESEARCH, Issue 6 2004
    Liselotte E. Jensen
    Abstract BACKGROUND There is compelling evidence that the risk of spina bifida, a malformation of the caudal neural tube, is associated with maternal and/or embryonic disturbances in folate/homocysteine metabolism. Hence, functional variants of genes that influence folate/homocysteine metabolism constitute a biologically plausible group of candidate risk factors for spina bifida and other neural tube defects. One such candidate is ABCC2, the gene encoding ABCC2, (a.k.a. canalicular multispecific organic anion transporter [cMOAT], multidrug resistance related protein 2 [MRP2]), a member of the ABC transporter family that effluxes natural folates and anti-folate drugs such as methotrexate. METHODS The association between the risk of spina bifida and both the maternal and embryonic ABCC2 C(,24)T genotype was evaluated by using the transmission disequilibrium test and log-linear modeling. RESULTS These analyses provided no evidence that the risk of spina bifida was significantly related to either the maternal or embryonic ABCC2 C(,24)T genotype. CONCLUSIONS The results of the present analyses suggest that the C(,24)T variant of the ABCC2 gene is not a major determinant of spina bifida risk. Birth Defects Research (Part A), 2004. © 2004 Wiley-Liss, Inc. [source]

    Expression of Drug Resistance-related Genes in Head and Neck Squamous Cell Carcinoma and Normal Mucosa

    CANCER SCIENCE, Issue 1 2000
    Shitau Hirata
    We examined the expression levels of mRNA for multidrug resistance 1 (MDR1), multidrug resistance-associated protein (MRP), human canalicular multispecific organic anion transporter (cMOAT), lung resistance-related protein (LRP), topoisomerase II,, ,(Topo II,, ,) and topoisomerase I (Topo I) genes in human head and neck squamous cell carcinoma (HNSCC) specimens and mucosa (HNM) specimens, to elucidate their roles in relation to the biological characteristics and drug resistance in vivo. Fifty-eight samples (45 head and neck carcinomas and 13 head and neck mucosa) obtained during surgical resection or biopsy from 38 patients were analyzed using the quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. MDR1, MRP, LRP, Topo II,, Topo II,, and Topo I gene transcripts were detected in all the samples tested, but cMOAT mRNA was not detected in them. Comparisons of the expression levels in HNSCC with those in HNM showed that the Topo II, gene expression level was higher in HNSCC than in HNM (P=0.0298). Moreover, the Topo II, mRNA level was significantly higher in metastatic lymph node samples of HNSCC than in HNM samples (P=0.0205). There were no significant differences in the six genes' expression levels between samples exposed to platinum drugs and those not exposed to platinum drugs. These results suggest that it may be effective in anticancer therapy to use topoisomerase-targetting drugs against HNSCC, especially metastatic neck tumors, and that the expression of these genes in HNSCC is not associated with platinum drug exposure. [source]

    Effects of proinflammatory cytokines on rat organic anion transporters during toxic liver injury and cholestasis

    HEPATOLOGY, Issue 2 2003
    Andreas Geier M.D.
    Hepatobiliary transporters are down-regulated in toxic and cholestatic liver injury. Cytokines such as tumor necrosis factor , (TNF-,) and interleukin 1, (IL-1,) are attributed to mediate this regulation, but their particular contribution in vivo is still unknown. Thus, we studied the molecular mechanisms by which Ntcp, Oatp1, Oatp2, and Mrp2 are regulated by proinflammatory cytokines during liver injury. Rats were injected intraperitoneally with either carbon tetrachloride or endotoxin. Inactivation of TNF-, and IL-1, was achieved by repetitive intraperitoneal injection of etanercept and anakinra, respectively. Messenger RNA (mRNA) levels of transporters and binding activities as well as nuclear protein levels of Ntcp, Oatp2, and Mrp2 transactivators were determined 20 to 24 hours later. In contrast to IL-1,, TNF-, inactivation alone fully prevented down-regulation of Ntcp, Oatp1, and Oatp2 mRNA as well as reduced binding activity of hepatocyte nuclear factor 1 (HNF-1) in CCl4 -induced toxic injury. In endotoxemia, down-regulation of Mrp2, and partially in case of Ntcp, could be prevented by IL-1, but not TNF-, blockade. However, inactivation of either cytokine led to preservation of HNF1 and partially of retinoid X receptor/retinoic acid receptor (RXR/RAR) binding activity. No effect of anticytokines was seen on pregnane X receptor (PXR) and constitutive androstane receptor (CAR) binding activity as well as nuclear protein mass. In conclusion, TNF-, represents the master cytokine responsible for HNF1-dependent down-regulation of Ntcp, Oatp1, and Oatp2 in CCl4 -induced toxic liver injury. IL-1, predominates in a complex signaling network of Ntcp and Mrp2 regulation in cholestatic liver injury. In contrast to in vitro studies, HNF1 and RXR/RAR-independent mechanisms appear to be more important in regulation of Mrp2 and Ntcp gene expression in endotoxemia. [source]

    Cultured mammary epithelial monolayers (BME-UV) express functional organic anion and cation transporters

    JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009
    M. M. AL-BATAINEH
    There is ongoing concern about the potential adverse effects of xenobiotic residues in cows' milk to the human consumer. Although drugs that are intentionally administered to lactating dairy cattle are rigorously regulated to prevent harmful residues, there are numerous other potential sources of exposure that are not as easily controlled. For example, cattle may be exposed to mycotoxins, pesticides and/or persistent organic pollutants through feed, water and inhalation of polluted air. Accurate estimates of the rate and extent of excretion of these compounds into milk is important to assess the risk of exposure through cows' milk. In the present study, the expression of carrier mediated transport processes in cultured monolayers of an immortalized bovine mammary epithelial cell line (BME-UV) was determined using a flow-through diffusion cell system, selective substrates and inhibitors of organic cation transporters (OCT) and organic anion transporters (OAT). The basal-to-apical (BL-to-Ap) flux of tetraethylammonium and estrone sulfate significantly exceeded their flux in the opposite direction. The addition of selective inhibitors to the donor compartment significantly decreased the BL-to-Ap flux of either selective substrate. These results suggest that both OCT and OAT are functionally expressed by BME-UV cells. [source]

    Towards an understanding of organic anion transporters: Structure,function relationships

    MEDICINAL RESEARCH REVIEWS, Issue 6 2004
    Guofeng You
    Abstract Organic anion transporters (OAT) play essential roles in the body disposition of clinically important anionic drugs, including anti-viral drugs, anti-tumor drugs, antibiotics, anti-hypertensives, and anti-inflammatories. The activities of OATs are directly linked to drug toxicity and drug,drug interactions. So far, four members of the OAT family have been identified: OAT1, OAT2, OAT3, and OAT4. These transporters share several common structural features including 12 transmembrane domains, multiple glycosylation sites localized in the first extracellular loop between transmembrane domains 1 and 2, and multiple phosphorylation sites present in the intracellular loop between transmembrane domains 6 and 7, and in the carboxyl terminus. The impact of these structural features on the function of these transporters has just begun to be explored. In the present review, the author will summarize recent progress made from her laboratory as well as from others, on the molecular characterization of the structure,function relationships of OATs, including particular amino acid residues/regions of the transporter protein ("molecular domains") that potentially determine transport characteristics. © 2004 Wiley Periodicals, Inc. Med Res Rev, 24, No. 6, 762,774, 2004 [source]

    Structure, function, and regulation of renal organic anion transporters

    MEDICINAL RESEARCH REVIEWS, Issue 6 2002
    Guofeng You
    Abstract Renal elimination of anionic drugs, xenobiotics, and toxins is necessary for the survival of mammalian species. This process is mediated by vectorial transport from blood to urine through the cooperative functions of specific transporters in the basolateral and apical membranes of the proximal tubule epithelium. The first step of this process is the extraction of organic anions from the peritubular blood plasma into proximal tubule cells largely through the organic anion transporter (OAT) pathway. Therefore, the OAT pathway is one of the major sites for body drug clearance/detoxification. As a result, it is also the site for drug,drug interaction and drug-induced nephrotoxicity. To maximize therapeutic efficacy and minimize toxicity, the structure-function relationships of OATs and their regulation must be defined. The recent cloning and identification of OATs have paved the way for such investigations. This review summarizes the available data on the general properties of OATs, focusing in particular on the recent progress made from the author's laboratory as well as from other's, on the molecular characterization of the structure-function relationships of OATs and their regulatory mechanisms. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 6, 602,616, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10019 [source]

    Nematicidal activity of anion transport blockers against Meloidogyne incognita, Caenorhabditis elegans and Heterorhabditis bacteriophora

    PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 6 2008
    Dhana Raj Boina
    Abstract BACKGROUND: Because methyl bromide has been phased out as a soil sterilant, new nematicides are urgently needed. Four different chemical classes of organic acids acting as anion transport (AT) blockers were tested against a free-living nematode, Caenorhabditis elegans Maupas, a plant-parasitic nematode, Meloidogyne incognita (Kofoid and White) Chitwood, and an entomopathogenic nematode, Heterorhabditis bacteriophora Poinar, in toxicity bioassays. The materials tested were DIDS (4,4,-diisothiocyanatostilbene-2,2,-disulfonic acid), 9-AC (anthracene-9-carboxylic acid), NPPB [5-nitro-2-(3-phenylpropylamino)benzoic acid] and IAA-94 (indanyloxyacetic acid). RESULTS: All the compounds showed slowly developing nematicidal activity against second-stage juveniles of M. incognita and adults of C. elegans, but not against H. bacteriophora infective-stage juveniles. The LC50 values of these compounds were < 50 mg L,1 after 48 and 72 h incubation, while at 168 h incubation the LC50 values were < 10 mg L,1 for both sensitive species. Across both species and time, the LC50 values generally differed no more than twofold among the four compounds tested in this study. In contrast, none of the compounds (200 mg L,1) caused more than control mortality to H. bacteriophora, even after 168 h of incubation. CONCLUSION: These compounds are potential leads for commercial nematicides. The insensitivity to H. bacteriophora is consistent with the natural exposure of this nematode to DST (3,5-dihydroxy-4-isopropylstilbene), a stilbene produced by its symbiotic bacterium. Based on the known activity of the compounds used in this study, it is suggested that anion transporters form the probable target sites for DIDS, 9-AC, NPPB and IAA-94 in nematodes. Copyright © 2008 Society of Chemical Industry [source]

    Diverse transport modes by the solute carrier 26 family of anion transporters

    THE JOURNAL OF PHYSIOLOGY, Issue 10 2009
    Ehud Ohana
    The solute carrier 26 (SLC26) transporters are anion transporters with diverse substrate specificity. Several members are ubiquitous while others show limited tissue distribution. They are expressed in many epithelia and to the extent known, play a central role in anion secretion and absorption. Members of the family are primarily Cl, transporters, although some members transport mainly SO42,, Cl,, HCO3, or I,. A defining feature of the family is their functional diversity. Slc26a1 and Slc26a2 function as specific SO42, transporters while Slc26a4 functions as an electroneutral Cl,/I,/HCO3, exchanger. Slc26a3 and Slc26a6 function as coupled electrogenic Cl,/HCO3, exchangers or as bona fide anion channels. SLC26A7 and SLC26A9 function exclusively as Cl, channels. This short review discusses the functional diversity of the SLC26 transporters. [source]

    Toxicity and disruption of midgut physiology in larvae of the European corn borer, Ostrinia nubilalis, by anion transporter blockers

    ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 3 2009
    Dhana Raj Boina
    Abstract In this study, four blockers of anion transporters (ATs) belonging to four different classes of organic acids, including DIDS (4, 4'-diisothiocyanatostilbene-2, 2'- disulfonic acid; a stilbene disulfonic acid), NPPB [(5-nitro-2-(3-phenylpropylamino) benzoic acid; an anthranilic acid)], 9-AC (anthracene-9-carboxylic acid; an aromatic carboxylic acid), and IAA-94 (indanyloxy acetic acid; an indanyloxy alkanoic acid), were tested for their toxicity against the European corn borer (ECB), Ostrinia nubilalis. All the AT blockers inhibited the growth of larvae, increased the developmental time, and decreased survival compared to controls, when second-instar ECB larvae were fed for seven days on treated diet. In general, DIDS and NPPB were the most active compounds, with the rank order of activity being DIDS>NPPB>IAA-94>9-AC. All the AT blockers decreased the midgut alkalinity in fifth-instar larvae when fed for 3,h on treated diet. Effective concentrations required for 50% decrease in midgut alkalinity (EC50) ranged between 29.1 and 41.2,ppm and the rank order of activity was NPPB>DIDS>IAA-94>9-AC. Similarly, all the tested AT blockers inhibited 36Cl, uptake from the midgut lumen in fifth-instar larvae when fed for 3,h on treated diet. Concentrations required for 50% inhibition of 36Cl, uptake (IC50) ranged between 7.4 and 11.0,ppm and the rank order of activity was DIDS>NPPB>9-AC >IAA-94. Modest to highly strong positive correlations observed among growth, midgut alkalinity, and midgut Cl, ion transport in AT blocker,fed larvae suggested that these effects are causally related to each other. Finally, AT blockers have the potential to become good candidates for development of insecticides with a unique mode of action. © 2009 Wiley Periodicals, Inc. [source]

    Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology

    BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2010
    Adam L. VanWert
    Abstract Our understanding of the mechanisms behind inter- and intra-patient variability in drug response is inadequate. Advances in the cytochrome P450 drug metabolizing enzyme field have been remarkable, but those in the drug transporter field have trailed behind. Currently, however, interest in carrier-mediated disposition of pharmacotherapeutics is on a substantial uprise. This is exemplified by the 2006 FDA guidance statement directed to the pharmaceutical industry. The guidance recommended that industry ascertain whether novel drug entities interact with transporters. This suggestion likely stems from the observation that several novel cloned transporters contribute significantly to the disposition of various approved drugs. Many drugs bear anionic functional groups, and thus interact with organic anion transporters (OATs). Collectively, these transporters are nearly ubiquitously expressed in barrier epithelia. Moreover, several reports indicate that OATs are subject to diverse forms of regulation, much like drug metabolizing enzymes and receptors. Thus, critical to furthering our understanding of patient- and condition-specific responses to pharmacotherapy is the complete characterization of OAT interactions with drugs and regulatory factors. This review provides the reader with a comprehensive account of the function and substrate profile of cloned OATs. In addition, a major focus of this review is on the regulation of OATs including the impact of transcriptional and epigenetic factors, phosphorylation, hormones and gender. Copyright © 2009 John Wiley & Sons, Ltd. [source]

    Role of multidrug resistance protein 2 (MRP2) in glutathione-bimane efflux from Caco-2 and rat renal proximal tubule cells

    BRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2001
    Sylvie A Terlouw
    The multidrug resistance protein 2 (MRP2) has been shown to play an important role in the transport of glutathione conjugates in the liver. Its importance in renal excretion, however, is still uncertain and other organic anion transporters may be involved. The objective of the present study was to characterize glutathione conjugate efflux from rat kidney proximal tubule cells (PTC), and to determine the contribution of Mrp2. We used isolated PTC in suspension, as well as grown to monolayer density. For comparison, transport characteristics were also determined in the human intestinal epithelial cell line Caco-2, an established model to study MRP2-mediated transport. The cells were loaded with monochlorobimane (MCB) at 10°C. MCB enters the cells by simple diffusion and is conjugated with glutathione to form the fluorescent glutathione-bimane (GS-B). In primary cultures of rat PTC, no indications for a transporter-mediated mechanism were found. The efflux of GS-B from Caco-2 cells and freshly isolated PTC was time- and temperature-dependent. Furthermore, GS-B transport in both models was inhibited by chlorodinitrobenzene (CDNB), with an inhibitory constant of 46.8±0.9 ,M in freshly isolated PTC. In Caco-2 cells, the inhibitory potency of CDNB was approximately 20 fold higher. Finally, efflux of GS-B from freshly isolated PTC from Mrp2-deficient (TR,) rats was studied. As compared to normal rat PTC, transport characteristics were not different. We conclude that in freshly isolated rat PTC glutathione conjugate excretion is mediated by other organic anion transporters rather than by Mrp2. British Journal of Pharmacology (2001) 134, 931,938; doi:10.1038/sj.bjp.0704284 [source]