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Pesquisa : D12.776.157.530.450.074.500.781.750 [Categoria DeCS]
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[PMID]:29273507
[Au] Autor:Furuya T; Takehara I; Shimura A; Kishimoto H; Yasujima T; Ohta K; Shirasaka Y; Yuasa H; Inoue K
[Ad] Endereço:Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
[Ti] Título:Organic anion transporter 1 (OAT1/SLC22A6) enhances bioluminescence based on d-luciferin-luciferase reaction in living cells by facilitating the intracellular accumulation of d-luciferin.
[So] Source:Biochem Biophys Res Commun;495(3):2152-2157, 2018 01 15.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bioluminescence (BL) imaging based on d-luciferin (d-luc)-luciferase reaction allows noninvasive and real-time monitoring of luciferase-expressing cells. Because BL intensity depends on photons generated through the d-luc-luciferase reaction, an approach to increase intracellular levels of d-luc could improve the detection sensitivity. In the present study, we showed that organic anion transporter 1 (OAT1) is useful, as a d-luc transporter, in boosting the BL intensity in luciferase-expressing cells. Functional screening of several transporters showed that the expression of OAT1 in HEK293 cells stably expressing Pyrearinus termitilluminans luciferase (HEK293/eLuc) markedly enhanced BL intensity in the presence of d-luc. When OAT1 was transiently expressed in HEK293 cells, intracellular accumulation of d-luc was higher than that in control cells, and the specific d-luc uptake mediated by OAT1 was saturable with a Michaelis constant (K ) of 0.23 µM. The interaction between OAT1 and d-luc was verified using 6-carboxyfluorescein, a typical substrate of OAT1, which showed that d-luc inhibited the uptake of 6-carboxyfluorescein mediated by OAT1. BL intensity was concentration-dependent at steady states in HEK293/eLuc cells stably expressing OAT1, and followed Michaelis-Menten kinetics with an apparent K of 0.36 µM. In addition, the enhanced BL was significantly inhibited by OAT1-specific inhibitors. Thus, OAT1-mediated transport of d-luc could be a rate-limiting step in the d-luc-luciferase reaction. Furthermore, we found that expressing OAT1 in HEK293/eLuc cells implanted subcutaneously in mice also significantly increased the BL after intraperitoneal injection of d-luc. Our findings suggest that because OAT1 is capable of transporting d-luc, it can also be used to improve visualization and monitoring of luciferase-expressing cells.
[Mh] Termos MeSH primário: Benzotiazóis/metabolismo
Aumento da Imagem/métodos
Luciferases/metabolismo
Medições Luminescentes/métodos
Proteína 1 Transportadora de Ânions Orgânicos/metabolismo
[Mh] Termos MeSH secundário: Genes Reporter/genética
Células HEK293
Seres Humanos
Luciferases/genética
Imagem Molecular/métodos
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Benzothiazoles); 0 (D-luciferin); 0 (Organic Anion Transport Protein 1); EC 1.13.12.- (Luciferases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171224
[St] Status:MEDLINE


  2 / 396 MEDLINE  
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[PMID]:28890383
[Au] Autor:Yuan Y; Yang H; Kong L; Li Y; Li P; Zhang H; Ruan J
[Ad] Endereço:College of Pharmaceutical Sciences, Soochow University, Suzhou, China; Department of Pharmacy, Wuxi Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, China.
[Ti] Título:Interaction between rhein acyl glucuronide and methotrexate based on human organic anion transporters.
[So] Source:Chem Biol Interact;277:79-84, 2017 Nov 01.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Rhein, a major bioactive compound of many medicinal herbs and the prodrug of diacerein, is often used with low dose of methotrexate as drug combination to treat rheumatoid arthritis. In this study, potential drug-drug interaction between methotrexate and rhein was investigated based on organic anion transporters (OAT). Our study demonstrated that rhein acyl glucuronide (RAG), the major metabolite of rhein in the human blood circulation, significantly inhibited the uptake of p-aminohippurate in hOAT1 transfected cells with IC value of 691 nM and estrone sulfate uptake in hOAT3 transfected cells with IC value of 78.5 nM. As the substrate of both hOAT1 and hOAT3, the methotrexate transport was significantly inhibited by RAG in hOAT1 transfected cells at 50 µM and hOAT3 transfected cells at 1 µM by 69% and 87%, respectively. Further in vivo study showed that after co-administrated with RAG in rats the AUC values of methotrexate increased from 3109 to 5370 ng/mL*hr and the t was prolonged by 40.5% (from 7.4 to 10.4 h), demonstrating the inhibitory effect of RAG on methotrexate excretion. In conclusion, rhein acyl glucuronide could significantly decrease the transport of methotrexate by both hOAT1 and hOAT3. The combination use of rhein, diacerein or other rhein-containing herbs with methotrexate may cause obvious drug-drug interaction and require close monitoring for potential drug interaction in clinical practice.
[Mh] Termos MeSH primário: Antraquinonas/farmacologia
Antirreumáticos/farmacocinética
Inibidores Enzimáticos/farmacologia
Glucuronídeos/farmacologia
Metotrexato/farmacocinética
Transportadores de Ânions Orgânicos/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Antraquinonas/metabolismo
Interações Medicamentosas
Inibidores Enzimáticos/metabolismo
Glucuronídeos/metabolismo
Células HEK293
Seres Humanos
Masculino
Proteína 1 Transportadora de Ânions Orgânicos/antagonistas & inibidores
Proteína 1 Transportadora de Ânions Orgânicos/metabolismo
Transportadores de Ânions Orgânicos/metabolismo
Transportadores de Ânions Orgânicos Sódio-Independentes/antagonistas & inibidores
Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthraquinones); 0 (Antirheumatic Agents); 0 (Enzyme Inhibitors); 0 (Glucuronides); 0 (Organic Anion Transport Protein 1); 0 (Organic Anion Transporters); 0 (Organic Anion Transporters, Sodium-Independent); 0 (SLC22A7 protein, human); YL5FZ2Y5U1 (Methotrexate); YM64C2P6UX (rhein)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE


  3 / 396 MEDLINE  
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[PMID]:28765282
[Au] Autor:Bush KT; Wu W; Lun C; Nigam SK
[Ad] Endereço:From the Departments of Pediatrics.
[Ti] Título:The drug transporter OAT3 (SLC22A8) and endogenous metabolite communication via the gut-liver-kidney axis.
[So] Source:J Biol Chem;292(38):15789-15803, 2017 Sep 22.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The organic anion transporters OAT1 (SLC22A6) and OAT3 (SLC22A8) have similar substrate specificity for drugs, but it is far from clear whether this holds for endogenous substrates. By analysis of more than 600 metabolites in the (Oat3 knockout) by LC/MS, we demonstrate OAT3 involvement in the movement of gut microbiome products, key metabolites, and signaling molecules, including those flowing through the gut-liver-kidney axis. Major pathways affected included those involved in metabolism of bile acids, flavonoids, nutrients, amino acids (including tryptophan-derivatives that are uremic toxins), and lipids. OAT3 is also critical in elimination of liver-derived phase II metabolites, particularly those undergoing glucuronidation. Analysis of physicochemical features revealed nine distinct metabolite groups; at least one member of most clusters has been previously validated in transport assays. In contrast to drugs interacting with the OATs, endogenous metabolites accumulating in the (Oat1 knockout) have distinct differences in their physicochemical properties; they are very different in size, number of rings, hydrophobicity, and molecular complexity. Consistent with the Remote Sensing and Signaling Hypothesis, the data support the importance of the OAT transporters in inter-organ and inter-organismal remote communication via transporter-mediated movement of key metabolites and signaling molecules ( gut microbiome-to-intestine-to-blood-to-liver-to-kidney-to-urine). We discuss the possibility of an intimate connection between OATs and metabolite sensing and signaling pathways ( bile acids). Furthermore, the metabolomics and pathway analysis support the view that OAT1 plays a greater role in kidney proximal tubule metabolism and OAT3 appears relatively more important in systemic metabolism, modulating levels of metabolites flowing through intestine, liver, and kidney.
[Mh] Termos MeSH primário: Intestinos/metabolismo
Rim/metabolismo
Fígado/metabolismo
Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo
[Mh] Termos MeSH secundário: Aminoácidos/metabolismo
Animais
Ácidos e Sais Biliares/metabolismo
Dieta
Metabolismo Energético
Microbioma Gastrointestinal
Técnicas de Inativação de Genes
Intestinos/microbiologia
Ligantes
Metabolismo dos Lipídeos
Masculino
Metabolômica
Camundongos
Camundongos Endogâmicos C57BL
Proteína 1 Transportadora de Ânions Orgânicos/metabolismo
Transportadores de Ânions Orgânicos Sódio-Independentes/deficiência
Transportadores de Ânions Orgânicos Sódio-Independentes/genética
Especificidade por Substrato
Xenobióticos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (Bile Acids and Salts); 0 (Ligands); 0 (Organic Anion Transport Protein 1); 0 (Organic Anion Transporters, Sodium-Independent); 0 (Slc22a6 protein, mouse); 0 (Xenobiotics); 0 (organic anion transport protein 3)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170803
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.796516


  4 / 396 MEDLINE  
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[PMID]:28630284
[Au] Autor:Burckhardt BC; Henjakovic M; Hagos Y; Burckhardt G
[Ad] Endereço:Center of Physiology and Pathophysiology, University Medical Center Goettingen, Goettingen, Germany (B.C.B, M.H., Y.H., G.B.); Department I of Internal Medicine, University Medical Center Cologne, Cologne, Germany (M.H.); and PortaCellTec Biosciences GmbH, Goettingen, Germany (Y.H.) birgitta.burckha
[Ti] Título:Differential Interaction of Dantrolene, Glafenine, Nalidixic Acid, and Prazosin with Human Organic Anion Transporters 1 and 3.
[So] Source:J Pharmacol Exp Ther;362(3):450-458, 2017 Sep.
[Is] ISSN:1521-0103
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In renal proximal tubule cells, the organic anion transporters 1 and 3 (OAT1 and OAT3) in the basolateral membrane and the multidrug resistance-associated protein 4 (MRP4) in the apical membrane share substrates and co-operate in renal drug secretion. We hypothesized that recently identified MRP4 inhibitors dantrolene, glafenine, nalidixic acid, and prazosin also interact with human OAT1 and/or OAT3 stably transfected in human embryonic kidney 293 cells. These four drugs were tested as possible inhibitors of -[ H]aminohippurate (PAH) and [ C]glutarate uptake by OAT1, and of [ H]estrone-3-sulfate (ES) uptake by OAT3. In addition, we explored whether these drugs decrease the equilibrium distribution of radiolabeled PAH, glutarate, or ES, an approach intended to indirectly suggest drug/substrate exchange through OAT1 and OAT3. With OAT3, a dose-dependent inhibition of [ H]ES uptake and a downward shift in [ H]ES equilibrium were observed, indicating that all four drugs bind to OAT3 and may possibly be translocated. In contrast, the interaction with OAT1 was more complex. With [ C]glutarate as substrate, all four drugs inhibited uptake but only glafenine and nalidixic acid shifted glutarate equilibrium. Using [ H]PAH as a substrate of OAT1, nalidixic acid inhibited but dantrolene, glafenine, and prazosin stimulated uptake. Nalidixic acid decreased equilibrium content of [ H]PAH, suggesting that it may possibly be exchanged by OAT1. Taken together, OAT1 and OAT3 interact with the MRP4 inhibitors dantrolene, glafenine, nalidixic acid, and prazosin, indicating overlapping specificities. At OAT1, more than one binding site must be assumed to explain substrate and drug-dependent stimulation and inhibition of transport activity.
[Mh] Termos MeSH primário: Dantroleno/metabolismo
Glafenina/metabolismo
Ácido Nalidíxico/metabolismo
Proteína 1 Transportadora de Ânions Orgânicos/metabolismo
Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo
Prazosina/metabolismo
[Mh] Termos MeSH secundário: Ligação Competitiva
Técnicas de Cultura de Células
Estrona/análogos & derivados
Estrona/metabolismo
Células HEK293
Seres Humanos
Taxa de Depuração Metabólica
Proteína 1 Transportadora de Ânions Orgânicos/genética
Transportadores de Ânions Orgânicos Sódio-Independentes/genética
Ligação Proteica
Ensaio Radioligante
Eliminação Renal
Especificidade por Substrato
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Organic Anion Transport Protein 1); 0 (Organic Anion Transporters, Sodium-Independent); 0 (organic anion transport protein 3); 2DI9HA706A (Estrone); 3B91HWA56M (Nalidixic Acid); 46HL4I09AH (Glafenine); F64QU97QCR (Dantrolene); QTL48N278K (estrone sulfate); XM03YJ541D (Prazosin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170621
[St] Status:MEDLINE
[do] DOI:10.1124/jpet.117.241406


  5 / 396 MEDLINE  
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[PMID]:28559139
[Au] Autor:Kawasaki T; Takeichi Y; Tomita M; Uwai Y; Epifano F; Fiorito S; Taddeo VA; Genovese S; Nabekura T
[Ad] Endereço:Department of Pharmaceutics, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650, Japan.
[Ti] Título:Effects of phenylpropanoids on human organic anion transporters hOAT1 and hOAT3.
[So] Source:Biochem Biophys Res Commun;489(4):375-380, 2017 Aug 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human organic anion transporters hOAT1/SLC22A6 and hOAT3/SLC22A8 are highly expressed on the basolateral membrane of renal proximal tubules and mediate tubular uptake of anionic drugs from blood. They play an important role for drug disposition, and therefore close studies of their ligand recognition are important for drug therapy and development. In this study, we performed uptake experiments using HEK293 and fluorescent anion 6-carboxyfluorescein to asses the effects of phenylpropanoids on hOAT1 and hOAT3. We found that phenylpropanoids, 3-(4'-isopentenyloxyphenyl)-benzoic acid (IBA), 3-(4'-isopentenyloxy-3'-methoxyphenyl)-benzoic acid (IMBA), and 3-(4'-geranyloxy-3'-methoxy phenyl)-benzoic acid (GMBA) inhibited hOAT1 and hOAT3. The K values for hOAT1 were comparable to that of probenecid, a strong inhibitor of hOAT1 and hOAT3. While IBA demonstrated competitive inhibition, IMBA and GMBA showed mixed-type inhibition. After preincubation and washout, the inhibitory effects remained with IMBA and GMBA but not IBA, suggesting that the functional group at 3'-position is responsible for these differences. In conclusion, IBA, IMBA, and GMBA are inhibitors of hOAT1 and hOAT3.
[Mh] Termos MeSH primário: Proteína 1 Transportadora de Ânions Orgânicos/antagonistas & inibidores
Transportadores de Ânions Orgânicos Sódio-Independentes/antagonistas & inibidores
Fenilpropionatos/farmacologia
[Mh] Termos MeSH secundário: Células Cultivadas
Relação Dose-Resposta a Droga
Células HEK293
Seres Humanos
Estrutura Molecular
Proteína 1 Transportadora de Ânions Orgânicos/metabolismo
Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo
Fenilpropionatos/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Organic Anion Transport Protein 1); 0 (Organic Anion Transporters, Sodium-Independent); 0 (Phenylpropionates); 0 (organic anion transport protein 3)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170601
[St] Status:MEDLINE


  6 / 396 MEDLINE  
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[PMID]:28472795
[Au] Autor:Favretto G; Souza LM; Gregório PC; Cunha RS; Maciel RAP; Sassaki GL; Toledo MG; Pecoits-Filho R; Souza WM; Stinghen AEM
[Ad] Endereço:Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba, Brazil.
[Ti] Título:Role of Organic Anion Transporters in the Uptake of Protein-Bound Uremic Toxins by Human Endothelial Cells and Monocyte Chemoattractant Protein-1 Expression.
[So] Source:J Vasc Res;54(3):170-179, 2017.
[Is] ISSN:1423-0135
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Organic anion transporters (OATs) are involved in the uptake of uremic toxins such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS), which play a role in endothelial dysfunction in patients with chronic kidney diseases (CKD). In this study, we investigated the role of OAT1 and OAT3 in the uptake of PCS and IS into human endothelial cells. PCS was synthesized via p-cresol sulfation and characterized using analytical methods. The cells were treated with PCS and IS in the absence and presence of probenecid (Pb), an OAT inhibitor. Cell viability was assessed using the MTT assay. The absorbed toxins were analyzed using chromatography, OAT expression using immunocytochemistry and western blot, and monocyte chemoattractant protein-1 (MCP-1) expression using enzyme-linked immunosorbent assay. Cell viability decreased after toxin treatment in a dose-dependent manner. PCS and IS showed significant internalization after 60 min treatment, while no internalization was observed in the presence of Pb, suggesting that OATs are involved in the transport of both toxins. Immunocytochemistry and western blot demonstrated OAT1 and OAT3 expression in endothelial cells. MCP-1 expression increased after toxins treatment but decreased after Pb treatment. PCS and IS uptake were mediated by OATs, and OAT blockage could serve as a therapeutic strategy to inhibit MCP-1 expression.
[Mh] Termos MeSH primário: Quimiocina CCL2/metabolismo
Células Endoteliais/metabolismo
Proteína 1 Transportadora de Ânions Orgânicos/metabolismo
Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo
Uremia/metabolismo
[Mh] Termos MeSH secundário: Transporte Biológico
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Cresóis/metabolismo
Cresóis/toxicidade
Relação Dose-Resposta a Droga
Células Endoteliais/efeitos dos fármacos
Células Endoteliais/patologia
Seres Humanos
Indicã/metabolismo
Indicã/toxicidade
Proteína 1 Transportadora de Ânions Orgânicos/antagonistas & inibidores
Transportadores de Ânions Orgânicos Sódio-Independentes/antagonistas & inibidores
Probenecid/farmacologia
Ésteres do Ácido Sulfúrico/metabolismo
Ésteres do Ácido Sulfúrico/toxicidade
Fatores de Tempo
Regulação para Cima
Uremia/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CCL2 protein, human); 0 (Chemokine CCL2); 0 (Cresols); 0 (Organic Anion Transport Protein 1); 0 (Organic Anion Transporters, Sodium-Independent); 0 (Sulfuric Acid Esters); 0 (organic anion transport protein 3); 56M34ZQY1S (4-cresol sulfate); N187WK1Y1J (Indican); PO572Z7917 (Probenecid)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1159/000468542


  7 / 396 MEDLINE  
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[PMID]:28371506
[Au] Autor:Tanner C; Boocock J; Stahl EA; Dobbyn A; Mandal AK; Cadzow M; Phipps-Green AJ; Topless RK; Hindmarsh JH; Stamp LK; Dalbeth N; Choi HK; Mount DB; Merriman TR
[Ad] Endereço:University of Otago, Dunedin, New Zealand.
[Ti] Título:Population-Specific Resequencing Associates the ATP-Binding Cassette Subfamily C Member 4 Gene With Gout in New Zealand Maori and Pacific Men.
[So] Source:Arthritis Rheumatol;69(7):1461-1469, 2017 Jul.
[Is] ISSN:2326-5205
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: There is no evidence for a genetic association between organic anion transporters 1-3 (SLC22A6, SLC22A7, and SLC22A8) and multidrug resistance protein 4 (MRP4; encoded by ABCC4) with the levels of serum urate or gout. The Maori and Pacific (Polynesian) population of New Zealand has the highest prevalence of gout worldwide. The aim of this study was to determine whether any Polynesian population-specific genetic variants in SLC22A6-8 and ABCC4 are associated with gout. METHODS: All participants had ≥3 self-reported Maori and/or Pacific grandparents. Among the total sample set of 1,808 participants, 191 hyperuricemic and 202 normouricemic individuals were resequenced over the 4 genes, and the remaining 1,415 individuals were used for replication. Regression analyses were performed, adjusting for age, sex, and Polynesian ancestry. To study the functional effect of nonsynonymous variants of ABCC4, transport assays were performed in Xenopus laevis oocytes. RESULTS: A total of 39 common variants were detected, with an ABCC4 variant (rs4148500) significantly associated with hyperuricemia and gout. This variant was monomorphic for the urate-lowering allele in Europeans. There was evidence for an association of rs4148500 with gout in the resequenced samples (odds ratio [OR] 1.62 [P = 0.012]) that was replicated (OR 1.25 [P = 0.033]) and restricted to men (OR 1.43 [P = 0.001] versus OR 0.98 [P = 0.89] in women). The gout risk allele was associated with fractional excretion of uric acid in male individuals (ß = -0.570 [P = 0.01]). A rare population-specific allele (P1036L) with predicted strong functional consequence reduced the uric acid transport activity of ABCC4 by 30%. CONCLUSION: An association between ABCC4 and gout and fractional excretion of uric acid is consistent with the established role of MRP4 as a unidirectional renal uric acid efflux pump.
[Mh] Termos MeSH primário: Gota/genética
Hiperuricemia/genética
Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética
Grupo com Ancestrais Oceânicos/genética
[Mh] Termos MeSH secundário: Adulto
Animais
Western Blotting
Estudos de Casos e Controles
Feminino
Seres Humanos
Modelos Logísticos
Masculino
Meia-Idade
Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo
Nova Zelândia
Oócitos/metabolismo
Proteína 1 Transportadora de Ânions Orgânicos/genética
Transportadores de Ânions Orgânicos Sódio-Independentes/genética
Polimorfismo de Nucleotídeo Único
Análise de Sequência de DNA
Ácido Úrico/metabolismo
Ácido Úrico/urina
Xenopus laevis
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCC4 protein, human); 0 (Multidrug Resistance-Associated Proteins); 0 (Organic Anion Transport Protein 1); 0 (Organic Anion Transporters, Sodium-Independent); 0 (SLC22A7 protein, human); 0 (organic anion transport protein 3); 268B43MJ25 (Uric Acid)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170821
[Lr] Data última revisão:
170821
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170404
[St] Status:MEDLINE
[do] DOI:10.1002/art.40110


  8 / 396 MEDLINE  
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[PMID]:28185988
[Au] Autor:Yu CP; Sweet DH; Peng YH; Hsieh YW; Chao PL; Hou YC; Lin SP
[Ad] Endereço:Department of Pharmacy, China Medical University Hospital, Taichung, Taiwan, ROC.
[Ti] Título:Effects of nonsteroidal anti-inflammatory drugs on the renal excretion of indoxyl sulfate, a nephro-cardiovascular toxin, in rats.
[So] Source:Eur J Pharm Sci;101:66-70, 2017 Apr 01.
[Is] ISSN:1879-0720
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Chronic kidney disease (CKD) is a health problem worldwide. Indoxyl sulfate (IS) is a nephro-cardiovascular toxin accumulated in CKD patients and cannot be removed through hemodialysis. The renal excretion of IS was mediated by organic anion transporters (OATs) OAT 1 and OAT 3. Because a number of nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to inhibit OATs, we hypothesize that NSAIDs might inhibit the renal excretion of IS. Rats were intravenously injected IS with and without diclofenac, ketoprofen or salicylic acid, individually. Blood samples were collected at predetermined time points and the concentrations of IS were determined by HPLC method. The results showed that diclofenac and ketoprofen at 10.0mg/kg significantly decreased the systemic clearance of IS by 71% and 82%, and increased the MRT of IS by 106% and 105%, respectively, whereas salicylic acid did not exhibit significant effects. Cell studies indicated that diclofenac and ketoprofen inhibited the uptake of IS mediated by OAT 1 and OAT 3. In conclusion, diclofenac and ketoprofen inhibited the excretion of IS through inhibition on OAT 1 and OAT 3.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/farmacologia
Sistema Cardiovascular/efeitos dos fármacos
Indicã/urina
Rim/efeitos dos fármacos
Eliminação Renal/efeitos dos fármacos
Toxinas Biológicas/urina
[Mh] Termos MeSH secundário: Animais
Células CHO
Linhagem Celular
Cricetulus
Diclofenaco/farmacologia
Cães
Células HEK293
Seres Humanos
Cetoprofeno/farmacologia
Rim/metabolismo
Células Madin Darby de Rim Canino
Masculino
Proteína 1 Transportadora de Ânions Orgânicos/metabolismo
Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo
Ratos
Ratos Sprague-Dawley
Ácido Salicílico/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Organic Anion Transport Protein 1); 0 (Organic Anion Transporters, Sodium-Independent); 0 (Toxins, Biological); 144O8QL0L1 (Diclofenac); 90Y4QC304K (Ketoprofen); N187WK1Y1J (Indican); O414PZ4LPZ (Salicylic Acid)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170621
[Lr] Data última revisão:
170621
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170211
[St] Status:MEDLINE


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[PMID]:27909713
[Au] Autor:Xu YJ; Wang Y; Lu YF; Xu SF; Wu Q; Liu J
[Ad] Endereço:Key Lab for Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
[Ti] Título:Age-associated differences in transporter gene expression in kidneys of male rats.
[So] Source:Mol Med Rep;15(1):474-482, 2017 Jan.
[Is] ISSN:1791-3004
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:Kidney transporters are involved in the secretion and reabsorption of endogenous and exogenous molecules. Numerous factors may influence their expression and affect drug disposition, efficacy and toxicity. The present study aimed to examine the development­ and age­associated variations in primary renal transporters in rats, including 6 uptake transporters: Organic anion transporter (OAT) 1 and 3, organic cation transporter (OCT) 1, 2 and 3 and organic anion­transporting polypeptide (OATP) 4C1, and 6 efflux transporters: Multidrug resistance protein 1 (MDR1), breast cancer resistance protein (BCRP), multidrug resistance­associated protein (MRP) 2 and 4, and multidrug and toxin extrusion protein (MATE) 1 and 2­K. Kidneys from male Sprague Dawley rats during development (­2, 1, 7, 14 and 21 days), maturation (28, 35 and 60 days) and aging (180, 540 and 850 days) were collected and total RNA was extracted, purified and subjected to reverse transcription­quantitative polymerase chain reaction analysis. Total proteins were extracted for western blot analysis. OAT1 and 3, OCT1, BCRP, MRP2 and 4 and MATE2­K expression levels were low in fetal kidneys, increased gradually following birth and markedly increased on maturation and adulthood. High levels were maintained until 850 days. OCT2, OATP4C1, Mdr1b and MATE1 expression levels were low in fetal kidneys, increased gradually following birth, and increased markedly on weaning, maturation and adulthood; however, levels were decreased on aging. OCT3 mRNA expression levels were low in fetal and newborn kidneys, and had two peaks at 35 and 850 days. The selected OAT1 and 3 and MDR1 protein expression levels revealed a similar expression pattern. Thus, kidney transporter expression is affected by ontogeny and aging, which may impact drug and toxicant disposition in children and the elderly.
[Mh] Termos MeSH primário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética
Envelhecimento
Regulação da Expressão Gênica
Rim/fisiologia
Transportadores de Ânions Orgânicos/genética
Proteínas de Transporte de Cátions Orgânicos/genética
[Mh] Termos MeSH secundário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética
Animais
Antiporters/genética
Rim/crescimento & desenvolvimento
Masculino
Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética
Proteína 1 Transportadora de Ânions Orgânicos/genética
RNA Mensageiro/análise
RNA Mensageiro/genética
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (Abcg2 protein, rat); 0 (Antiporters); 0 (MATE1 protein, rat); 0 (Multidrug Resistance-Associated Proteins); 0 (Organic Anion Transport Protein 1); 0 (Organic Anion Transporters); 0 (Organic Cation Transport Proteins); 0 (RNA, Messenger); 0 (Slc22a6 protein, rat); 0 (organic anion transporting polypeptide 4C1, rat)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161203
[St] Status:MEDLINE
[do] DOI:10.3892/mmr.2016.5970


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[PMID]:27485257
[Au] Autor:Qin Z; Zhao L; Hu H; Jiang H; Yu L; Zeng S
[Ad] Endereço:a Institute of Drug Metabolism and Pharmaceutical Analysis, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou , China.
[Ti] Título:Utilizing single- and double-transfected cell models expressing human organic anion transporter 1 and human cytochrome P450 1A2 to investigate the interactions with ingredients of herbal medicines.
[So] Source:Xenobiotica;47(7):576-583, 2017 Jul.
[Is] ISSN:1366-5928
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:1. Cell models expressing human drug transporters and enzymes are useful tools to understand the process of drug disposition in vitro. However, no study on transfected cells stably co-expressing human organic anion transporter 1 (hOAT1) and/or human cytochrome P450 1A2 (hCYP1A2) is available. In this study, cell models stably expressing hOAT1 and/or hCYP1A2 were established, and were used to investigate the interactions of ingredients of herbal medicines (IHMs) with hOAT1 and/or hCYP1A2. 2. The MDCK cells were stable transfected with recombinant plasmids expressing hOAT1 and/or hCYP1A2. Cellular uptake assay and CYP450 activity assay showed that the transfected cells were available. A marked high expression of hOAT1 and hCYP1A2 mRNA was also validated by quantitative RT-PCR. Totally 6 IHMs which significantly inhibited the activity of hOAT1 were screened out by employing hOAT1 expressing cells. The contribution of hOAT1 and hCYP1A2 to the toxicity of aristolochic acid I (AAI) was further determined. Compared to mock cells, all transfected cells showed a decrease in viability after being treated with AAI. 3. A method to establish transfected cell expressing drug metabolism enzymes and/or transporters was provided in our study. Three IHMs (dihydrotanshinone I, cryptotanshinone, and tanshinone I) were confirmed as novel inhibitors of hOAT1. Furthermore, a synergistic effect of hOAT1 and hCYP1A2 on AAI-induced toxicity was also observed in this investigation.
[Mh] Termos MeSH primário: Citocromo P-450 CYP1A2/metabolismo
Interações Ervas-Drogas
Modelos Biológicos
Proteína 1 Transportadora de Ânions Orgânicos/metabolismo
[Mh] Termos MeSH secundário: Animais
Transporte Biológico
Cães
Medicina Herbária
Seres Humanos
Células Madin Darby de Rim Canino
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Organic Anion Transport Protein 1); EC 1.14.14.1 (Cytochrome P-450 CYP1A2)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160804
[St] Status:MEDLINE
[do] DOI:10.1080/00498254.2016.1211774



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