The Experts below are selected from a list of 162 Experts worldwide ranked by ideXlab platform
Frans G. M. Russel - One of the best experts on this subject based on the ideXlab platform.
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Regulatory Pathways for ATP-binding Cassette Transport Proteins in Kidney Proximal Tubules
The AAPS journal, 2012Co-Authors: Rosalinde Masereeuw, Frans G. M. RusselAbstract:The ATP-binding cassette transport proteins (ABC transporters) represent important determinants of Drug Excretion. Protective or excretory tissues where these transporters mediate substrate efflux include the kidney proximal tubule. Regulation of the transport proteins in this tissue requires elaborate signaling pathways, including genetic, epigenetic, nuclear receptor mediated, posttranscriptional gene regulation involving microRNAs, and non-genomic (kinases) pathways triggered by hormones and/or growth factors. This review discusses current knowledge on regulatory pathways for ABC transporters in kidney proximal tubules, with a main focus on P-glycoprotein, multiDrug resistance proteins 2 and 4, and breast cancer resistance protein. Insight in these processes is of importance because variations in transporter activity due to certain (disease) conditions could lead to significant changes in Drug efficacy or toxicity.
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mechanisms and clinical implications of renal Drug Excretion
Drug Metabolism Reviews, 2001Co-Authors: Rosalinde Masereeuw, Frans G. M. RusselAbstract:The body defends itself against potentially harmful compounds like Drugs, toxic compounds, and their metabolites by elimination, in which the kidney plays an important role. Renal clearance is used to determine renal elimination mechanisms of a Drug, which is the result of glomerular filtration, active tubular secretion and reabsorption. The renal proximal tubule is the primary site of carrier-mediated transport from blood to urine. Renal secretory mechanisms exists for, anionic compounds and organic cations. Both systems comprises several transport proteins, and knowledge of the molecular identity of these transporters and their substrate specificity has increased considerably in the past decade. Due to overlapping specificities of the transport proteins, Drug interactions at the level of tubular secretion is an event that may occur in clinical situation. This review describes the different processes that determine renal Drug handling, the techniques that have been developed to attain more insight in the various aspects of Drug Excretion, the functional characteristics of the individual transport proteins, and finally the implications of Drug interactions in a clinical perspective.
Rosalinde Masereeuw - One of the best experts on this subject based on the ideXlab platform.
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Regulatory Pathways for ATP-binding Cassette Transport Proteins in Kidney Proximal Tubules
The AAPS journal, 2012Co-Authors: Rosalinde Masereeuw, Frans G. M. RusselAbstract:The ATP-binding cassette transport proteins (ABC transporters) represent important determinants of Drug Excretion. Protective or excretory tissues where these transporters mediate substrate efflux include the kidney proximal tubule. Regulation of the transport proteins in this tissue requires elaborate signaling pathways, including genetic, epigenetic, nuclear receptor mediated, posttranscriptional gene regulation involving microRNAs, and non-genomic (kinases) pathways triggered by hormones and/or growth factors. This review discusses current knowledge on regulatory pathways for ABC transporters in kidney proximal tubules, with a main focus on P-glycoprotein, multiDrug resistance proteins 2 and 4, and breast cancer resistance protein. Insight in these processes is of importance because variations in transporter activity due to certain (disease) conditions could lead to significant changes in Drug efficacy or toxicity.
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mechanisms and clinical implications of renal Drug Excretion
Drug Metabolism Reviews, 2001Co-Authors: Rosalinde Masereeuw, Frans G. M. RusselAbstract:The body defends itself against potentially harmful compounds like Drugs, toxic compounds, and their metabolites by elimination, in which the kidney plays an important role. Renal clearance is used to determine renal elimination mechanisms of a Drug, which is the result of glomerular filtration, active tubular secretion and reabsorption. The renal proximal tubule is the primary site of carrier-mediated transport from blood to urine. Renal secretory mechanisms exists for, anionic compounds and organic cations. Both systems comprises several transport proteins, and knowledge of the molecular identity of these transporters and their substrate specificity has increased considerably in the past decade. Due to overlapping specificities of the transport proteins, Drug interactions at the level of tubular secretion is an event that may occur in clinical situation. This review describes the different processes that determine renal Drug handling, the techniques that have been developed to attain more insight in the various aspects of Drug Excretion, the functional characteristics of the individual transport proteins, and finally the implications of Drug interactions in a clinical perspective.
Masereeuw R. - One of the best experts on this subject based on the ideXlab platform.
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The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane
International Society of Nephrology. Published by Elsevier Inc., 2008Co-Authors: Huls M., Brown C.d.a., Windass A.s., Sayer R., Van Den Heuvel J.j.m.w., Heemskerk S., Russel F.g.m., Masereeuw R.Abstract:The Breast Cancer Resistance Protein (BCRP/ABCG2) is a transporter restricting absorption and enhancing Excretion of many compounds including anticancer Drugs. This transporter is highly expressed in many tissues; however, in human kidney, only the mRNA was found in contrast to the mouse kidney, where the transporter is abundant. In bcrp/abcg2(−/−) mice, the expression of two sterol transporter genes, abcg5 and abcg8, was strongly increased in the kidney, perhaps as a compensatory mechanism to upregulate efflux. We found using immunohistochemical analysis clear localization of BCRP/ABCG2 to the proximal tubule brush border membrane of the human kidney comparable to that of other ABC transporters such as P-glycoprotein/ABCB1, MRP2/ABCC2, and MRP4/ABCC4. Hoechst 33342 dye efflux from primary human proximal tubule cells was significantly reduced by the BCRP/ABCG2 inhibitors fumitremorgin C and nelfinavir. Our study shows that in addition to other apical ABC transporters, BCRP/ABCG2 may be important in renal Drug Excretion
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The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane.
'Springer Science and Business Media LLC', 2008Co-Authors: Huls M., Windass A.s., Sayer R., Heemskerk S., Russel F.g.m., Masereeuw R., Brown C.d., Heuvel, J.j.m.w. Van DenAbstract:Contains fulltext : 70782.pdf (publisher's version ) (Closed access)The Breast Cancer Resistance Protein (BCRP/ABCG2) is a transporter restricting absorption and enhancing Excretion of many compounds including anticancer Drugs. This transporter is highly expressed in many tissues; however, in human kidney, only the mRNA was found in contrast to the mouse kidney, where the transporter is abundant. In bcrp/abcg2((-/-)) mice, the expression of two sterol transporter genes, abcg5 and abcg8, was strongly increased in the kidney, perhaps as a compensatory mechanism to upregulate efflux. We found using immunohistochemical analysis clear localization of BCRP/ABCG2 to the proximal tubule brush border membrane of the human kidney comparable to that of other ABC transporters such as P-glycoprotein/ABCB1, MRP2/ABCC2, and MRP4/ABCC4. Hoechst 33342 dye efflux from primary human proximal tubule cells was significantly reduced by the BCRP/ABCG2 inhibitors fumitremorgin C and nelfinavir. Our study shows that in addition to other apical ABC transporters, BCRP/ABCG2 may be important in renal Drug Excretion
Atsushi Fukatsu - One of the best experts on this subject based on the ideXlab platform.
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expression levels of renal organic anion transporters oats and their correlation with anionic Drug Excretion in patients with renal diseases
Pharmaceutical Research, 2004Co-Authors: Yuji Sakurai, Hideyuki Motohashi, Harumasa Ueo, Satohiro Masuda, Hideyuki Saito, Masahiro Okuda, Noriko Mori, Motokazu Matsuura, Toshio Doi, Atsushi FukatsuAbstract:Purpose. Because the urinary Excretion of Drugs is often decreased in renal diseases, dosage regimens are adjusted to avoid adverse Drug reactions. The aim of present study was to clarify the alteration in the levels of renal Drug transporters and their correlation with the urinary Drug Excretion in renal diseases patients.
Hermann Koepsell - One of the best experts on this subject based on the ideXlab platform.
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Drug Excretion mediated by a new prototype of polyspecific transporter
Nature, 1994Co-Authors: Dirk Grundemann, Valentin Gorboulev, Stepan Gambaryan, Maike Veyhl, Hermann KoepsellAbstract:CATIONIC Drugs of different types and structures (antihistaminics, antiarrhythmics, sedatives, opiates, cytostatics and antibiotics, for example) are excreted in mammals by epithelial cells of the renal proximal tubules and by hepatocytes in the liverl–4. In the proximal tubules, two functionally disparate transport systems are involved which are localized in the basolateral and luminal plasma membrane and are different from the previously identified neuronal monoamine transporters and ATP-dependent multiDrug exporting proteins1–3,5–12. Here we report the isolation of a complementary DNA from rat kidney that encodes a 556-amino-acid membrane protein, OCT1, which has the functional characteristics of organic cation uptake over the basolateral membrane of renal proximal tubules and of organic cation uptake into hepatocytes. OCT1 is not homologous to any other known protein and is found in kidney, liver and intestine. As OCT1 translocates hydrophobic and hydrophilic organic cations of different structures, it is considered to be a new prototype of polyspecific transporters that are important for Drug elimination.
