Impact of the induced organic anion transporter 1 (Oat1) renal expression by furosemide on the pharmacokinetics of organic anions

Nephrology ◽  
2017 ◽  
Vol 22 (8) ◽  
pp. 642-648 ◽  
Author(s):  
María Julia Severin ◽  
María Herminia Hazelhoff ◽  
Romina Paula Bulacio ◽  
María Eugenia Mamprin ◽  
Anabel Brandoni ◽  
...  
Keyword(s):  
Organic Anion ◽  
Organic Anions ◽  
Organic Anion Transporter ◽  
Anion Transporter ◽  
Renal Expression

scholarly journals Olfactory mucosa-expressed organic anion transporter, Oat6, manifests high affinity interactions with odorant organic anions

2006 ◽  
Vol 351 (4) ◽  
pp. 872-876 ◽  
Author(s):  
Gregory Kaler ◽  
David M. Truong ◽  
Derina E. Sweeney ◽  
Darren W. Logan ◽  
Megha Nagle ◽  
...  
Keyword(s):  
Organic Anion ◽  
Organic Anions ◽  
Olfactory Mucosa ◽  
Organic Anion Transporter ◽  
High Affinity ◽  
Anion Transporter

Effect of erythropoietin on mercury-induced nephrotoxicity: Role of membrane transporters

2020 ◽  
pp. 096032712095810
Author(s):  
MH Hazelhoff ◽  
AM Torres
Keyword(s):  
Renal Function ◽  
Organic Anion ◽  
Absorption Spectrometry ◽  
Renal Tissue ◽  
Mercury Content ◽  
Organic Anion Transporter ◽  
Tubular Injury ◽  
Human Erythropoietin ◽  
Anion Transporter ◽  
Renal Expression

Mercury is a widespread pollutant. Mercuric ions uptake into tubular cells is supported by the Organic anion transporter 1 (Oat1) and 3 (Oat3) and its elimination into urine is through the Multidrug resistance-associated protein 2 (Mrp2). We investigated the effect of recombinant human erythropoietin (Epo) on renal function and on renal expression of Oat1, Oat3, and Mrp2 in a model of mercuric chloride (HgCl2)-induced renal damage. Four experimental groups of adult male Wistar rats were used: Control, Epo, HgCl2, and Epo + HgCl2. Epo (3000 IU/kg, b.w., i.p.) was administered 24 h before HgCl2 (4 mg/kg, b.w., i.p.). Experiments were performed 18 h after the HgCl2 dose. Parameters of renal function and structure were evaluated. The protein expression of Oat1, Oat3 and Mrp2 in renal tissue was assessed by immunoblotting techniques. Mercury levels were determined by cold vapor atomic absorption spectrometry. Pretreatment with Epo ameliorated the HgCl2-induced tubular injury as assessed by histopathology and urinary biomarkers. Immunoblotting showed that pretreatment with Epo regulated the renal expression of mercury transporters in a way to decrease mercury content in the kidney. Epo pretreatment ameliorates HgCl2-induced renal tubular injury by modulation of mercury transporters expression in the kidneys.

Cisplatin induces renal expression of P-glycoprotein and canalicular multispecific organic anion transporter

1999 ◽  
Vol 277 (6) ◽  
pp. F832-F840 ◽  
Author(s):  
Michel Demeule ◽  
Mathieu Brossard ◽  
Richard Béliveau
Keyword(s):  
Chemotherapeutic Agent ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Rat Tissues ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Anion Transporter ◽  
Renal Brush Border Membranes ◽  
Renal Expression ◽  
Renal Brush Border

The expression of two members of the ATP-binding cassette family of transport proteins, P-glycoprotein (P-gp) and the canalicular multispecific organic anion transporter (cMOAT or Mrp2), was evaluated in renal brush-border membranes (BBM) and various rat tissues after cisplatin treatment. One administration of cisplatin (5 mg/kg) increased P-gp expression by >200–300% in renal BBM and in crude membranes from liver and intestine. The increase in P-gp expression in the kidney was also detected in photolabeling experiments, suggesting the induction of functional P-gp. cMOAT expression was increased by >10-fold in renal BBM after cisplatin administration, although it had no effect on liver cMOAT expression. The increase in the levels of both proteins was maximal at 2 days after cisplatin treatment and lasted for at least 8 days. These results indicate that a single administration of cisplatin induces overexpression of P-gp and cMOAT in specific tissues. This may be of significant relevance to the design of clinical trials using cisplatin as a single chemotherapeutic agent or in combination with other drugs.

Molecular Physiology of Renal p-Aminohippurate Secretion

Physiology ◽  
2001 ◽  
Vol 16 (3) ◽  
pp. 114-118 ◽  
Author(s):  
Gerhard Burckhardt ◽  
Andrew Bahn ◽  
Natascha A. Wolff
Keyword(s):  
Organic Anion ◽  
Organic Anions ◽  
Proximal Tubules ◽  
Organic Anion Transporter ◽  
Molecular Physiology ◽  
Renal Proximal Tubules ◽  
Anion Transporter ◽  
Tubule Lumen ◽  
Tubule Cells ◽  
Species Specific

Renal proximal tubules secrete various organic anions, including drugs and p-aminohippurate (PAH). Uptake of PAH from blood into tubule cells occurs by exchange with intracellular α-ketoglutarate and is mediated by the organic anion transporter 1. PAH exit into tubule lumen is species specific and may involve ATP-independent and -dependent transporters.

scholarly journals Organic Anion Transporter 5 Renal Expression and Urinary Excretion in Rats with Vascular Calcification

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
María Herminia Hazelhoff ◽  
Romina Paula Bulacio ◽  
Adriana Mónica Torres
Keyword(s):  
Urinary Excretion ◽  
Vascular Calcification ◽  
Western Blotting ◽  
Renal Injury ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Protein Levels ◽  
Anion Transporter ◽  
Male Wistar Rats ◽  
Renal Expression

It has been described renal damage in rats with vascular calcification. The organic anion transporter 5 (Oat5) is only expressed in kidney, and its urinary excretion was proposed as potential early biomarker of renal injury. The aim of this study was to evaluate the Oat5 renal expression and its urinary excretion in an experimental model of vascular calcification in comparison with traditional markers of renal injury. Vascular calcification was obtained by the administration of an overdose of vitamin D3(300,000 IU/kg, b.w., i.m.) to male Wistar rats. Oat5 urinary abundance was evaluated by Western blotting. Traditional markers of renal injury, such as creatinine and urea plasma levels, urinary protein levels, and urinary alkaline phosphatase (AP) activity, were determined using commercial kits. Histology was assessed by hematoxylin/eosin staining. Oat5 renal expression was evaluated by Western blotting and by immunohistochemistry. An increased expression of Oat5 in renal homogenates, in apical membranes, and in its urinary excretion was observed in rats with vascular calcification. The traditional parameters used to evaluate renal function were not modified, with the exception of histology. It is possible to postulate the urinary excretion of Oat5 as a potential noninvasive biomarker of renal injury associated with vascular calcification.

scholarly journals Immunohistochemical Localization of Multispecific Renal Organic Anion Transporter 1 in Rat Kidney

1999 ◽  
Vol 10 (3) ◽  
pp. 464-471 ◽  
Author(s):  
AKIHIRO TOJO ◽  
TAKASHI SEKINE ◽  
NORIKO NAKAJIMA ◽  
MAKOTO HOSOYAMADA ◽  
YOSHIKATSU KANAI ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Organic Anion ◽  
Basolateral Membrane ◽  
Organic Anions ◽  
Proximal Tubules ◽  
Organic Anion Transporter ◽  
Electron Microscopic ◽  
Renal Vasculature ◽  
Initial Portion ◽  
Anion Transporter

Abstract. Renal proximal convoluted tubules have an important role, i.e., to excrete organic anions, including numerous drugs and endogenous substances. Recently, multispecific organic anion transporter 1 (OAT1) was isolated from rat kidney. In this study, the cellular and subcellular localization of OAT1 in rat kidney was investigated. Kidneys from normal rats were perfused and fixed with periodate-lysine-paraformaldehyde solution and were then processed for immunohistochemical analysis using the labeled streptavidin-biotin method, preembedding horseradish peroxidase method, and immunogold method. Light microscopic examination revealed immunostaining for OAT1 in the middle portion of the proximal tubule (S2 segment), but not in the initial portion of the proximal convoluted tubule, next to the glomerulus. Nephron segments other than the S2 segment and the renal vasculature were not stained with antibody to OAT1. Electron-microscopic observation using a preembedding method revealed that OAT1 was exclusively expressed in the basolateral membrane of S2 segments of proximal tubules. The immunogold method showed no labeling for OAT1 in the cytoplasmic vesicles, suggesting that OAT1 may not move together with organic anions into the cells. These results are consistent with previous physiologic data showing that organic anions, including para-aminohippurate, are taken up by the basolateral Na+-independent organic anion/dicarboxylate exchanger and excreted at S2 segments. In conclusion, OAT1 was localized to the basolateral membrane of S2 segments of proximal tubules in rat kidneys.

Molecular cloning of canalicular multispecific organic anion transporter defective in EHBR

1997 ◽  
Vol 272 (1) ◽  
pp. G16-G22 ◽  
Author(s):  
K. Ito ◽  
H. Suzuki ◽  
T. Hirohashi ◽  
K. Kume ◽  
T. Shimizu ◽  
...  
Keyword(s):  
Amino Acid ◽  
Stop Codon ◽  
Organic Anion ◽  
Amino Acid Level ◽  
Premature Stop Codon ◽  
Autosomal Recessive Inheritance ◽  
Organic Anions ◽  
Organic Anion Transporter ◽  
Sprague Dawley ◽  
Anion Transporter

Several organic anions are excreted into the bile via a canalicular multispecific organic anion transporter (cMOAT), which is hereditarily defective in mutant rats, such as the Eisai hyperbilirubinemic rat (EHBR) and TR- rat. In the present study, we cloned cMOAT from the Sprague-Dawley rat liver cDNA library based on the homology with human multidrug resistance-associated protein (hMRP). cMOAT was encoded by 4,623-base pair (bp) cDNA with a homology of 53.0 and 46.3% with hMRP at the cDNA and deduced amino acid level, respectively. The deduced amino acid sequence was the same as that cloned in Wistar rats (C. C. Paulusma, P. J. Bosma, G. J. Zaman, C. T. Bakker, M. Otter, G. L. Sceffer, P. Borst, and R. P. Oude Elferink. Science Wash. DC 271: 1126, 1996) except for four amino acid substitutions. By screening the library, three kinds of cDNA species for cMOAT with the same open reading frame and different 3'-untranslated region lengths (0.2, 1.5, and 3.5 kbp) were isolated. The Northern blot analysis of poly(A)+ RNA from the liver revealed that the expression of plural bands (approximately 5, 6, and 8 kb) was defective in EHBR, and this may be due to the presence of these cDNA species. Expression of cMOAT was observed almost exclusively in the liver and to a lesser extent in the duodenum, kidney, and jejunum. Reverse transcription-polymerase chain reaction (RT-PCR) and subsequent sequence analysis of EHBR liver, kidney, duodenum, and jejunum revealed that 1-bp replacement from G to A at nucleotide 2564 resulted in the introduction of the premature stop codon in all tissues examined. This mutation was different from that observed in TR (C. C. Paulusma, P. J. Bosma, G. J. Zaman, C. T. Bakker, M. Otter, G. L. Sceffer, P. Borst, and R. P. Oude Elferink. Science Wash. DC 271: 1126, 1996). Because EHBR and TR- are allelic mutants and both strains exhibit an autosomal recessive inheritance in the biliary excretion of organic anions it was concluded that the impaired expression of this particular protein is related to the pathogenesis of hyperbilirubinemia in the mutant animals.

Molecular physiology of renal organic anion transporters

2006 ◽  
Vol 290 (2) ◽  
pp. F251-F261 ◽  
Author(s):  
Takashi Sekine ◽  
Hiroki Miyazaki ◽  
Hitoshi Endou
Keyword(s):  
Organic Anion ◽  
Organic Anions ◽  
Organic Anion Transporter ◽  
Transepithelial Transport ◽  
Gene Localization ◽  
Organic Anion Transporters ◽  
Molecular Physiology ◽  
Anion Transporters ◽  
Anion Transporter ◽  
Molecular Information

Recent advances in molecular biology have identified three organic anion transporter families: the organic anion transporter (OAT) family encoded by SLC22A, the organic anion transporting peptide (OATP) family encoded by SLC21A ( SLCO), and the multidrug resistance-associated protein (MRP) family encoded by ABCC. These families play critical roles in the transepithelial transport of organic anions in the kidneys as well as in other tissues such as the liver and brain. Among these families, the OAT family plays the central role in renal organic anion transport. Knowledge of these three families at the molecular level, such as substrate selectivity, tissue distribution, and gene localization, is rapidly increasing. In this review, we will give an overview of molecular information on renal organic anion transporters and describe recent topics such as the regulatory mechanisms and molecular physiology of urate transport. We will also discuss the physiological roles of each organic anion transporter in the light of the transepithelial transport of organic anions in the kidneys.

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