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

Rosuvastatin is a high affinity substrate of hepatic organic anion transporter OATP-C

2001 ◽  
Vol 2 (2) ◽  
pp. 90 ◽  
Author(s):  
C.D.A. Brown ◽  
A. Windass ◽  
K. Bleasby ◽  
B. Lauffart
Keyword(s):  
Organic Anion ◽  
Organic Anion Transporter ◽  
High Affinity ◽  
Anion Transporter

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

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 Novel properties of hepatic canalicular reduced glutathione transport revealed by radiation inactivation

1998 ◽  
Vol 274 (5) ◽  
pp. G923-G930 ◽  
Author(s):  
Aravind V. Mittur ◽  
Neil Kaplowitz ◽  
Ellis S. Kempner ◽  
Murad Ookhtens
Keyword(s):  
Organic Anion ◽  
Membrane Vesicles ◽  
Organic Anion Transporter ◽  
Initial Increase ◽  
Radiation Inactivation ◽  
High Affinity ◽  
Anion Transporter ◽  
Sigmoidal Kinetics ◽  
Single Exponential Function ◽  
Functional Size

Transport of GSH at the canalicular pole of hepatocytes occurs by a facilitative carrier and can account for ∼50% of total hepatocyte GSH efflux. A low-affinity unit with sigmoidal kinetics accounts for 90% of canalicular transport at physiological GSH concentrations. A low-capacity transporter with high affinity for GSH has also been reported. It is not known whether the same or different proteins mediate low- and high-affinity GSH transport, although they do differ in inhibitor specificity. The bile of rats with a mutation in the canalicular multispecific organic anion transporter (cMOAT or MRP-2, a 170-kDa protein) is deficient in GSH, implying that cMOAT may transport GSH. However, transport of GSH in canalicular membrane vesicles (CMV) from these mutant rats remains intact. We examined the functional size of the two kinetic components of GSH transport by radiation inactivation of GSH uptake in rat hepatic CMV. High-affinity transport of GSH was inactivated as a single exponential function of radiation dose, yielding a functional size of ∼70 kDa. In contrast, low-affinity canalicular GSH transport exhibited a complex biexponential response to irradiation, characterized by an initial increase followed by a decrease in GSH transport. Inactivation analysis yielded a ∼76-kDa size for the low-affinity transporter. The complex inactivation indicated that the low-affinity transporter is associated with a larger protein of ∼141 kDa, which masked ∼80% of the potential transport activity in CMV. Additional studies, using inactivation of leukotriene C4 transport, yielded a functional size of ∼302 kDa for cMOAT, indicating that it functions as a dimer.

scholarly journals MOAT4, a novel multispecific organic-anion transporter for glucuronides and mercapturates in mouse L1210 cells and human erythrocytes

1996 ◽  
Vol 320 (1) ◽  
pp. 273-281 ◽  
Author(s):  
Manju SAXENA ◽  
Gary B HENDERSON
Keyword(s):  
Transport System ◽  
Organic Anion ◽  
High Sensitivity ◽  
Human Erythrocytes ◽  
Organic Anion Transporter ◽  
High Affinity ◽  
L1210 Cells ◽  
Anion Transporter ◽  
Dependent Transport ◽  
Inside Out

Glucuronides and mercapturates were examined as possible high-affinity substrates for a low-affinity ATP-dependent transport system for 2,4-dinitrophenyl S-glutathione (DNP-SG) in mouse L1210 cells. Initial inhibitor studies with inside-out vesicles revealed that the low-affinity transport of [3H]DNP-SG (Km 450 µM) exhibits a high sensitivity to N-acetyl 2,4-dinitrophenyl cysteine (NAc-DNP-Cys) (Ki 5.0 µM) and α-naphthyl β-D-glucuronide (naphthyl glucuronide) (Ki 8.5 µM). Direct transport measurements showed the presence of ATP-dependent uptake activities for NAc-DNP-[35S]Cys and naphthyl [14C] glucuronide, and Km values for half-maximal transport were comparable to the Ki values of these compounds for inhibition of [3H]DNP-SG transport. Transport of [3H]DNP-SG, NAc-DNP-[35S]Cys and naphthyl [14 C]glucuronide each showed the same sensitivity to various anions and anion conjugates. Inhibition was competitive and was most potent for bilirubin ditaurate, indoprofen, 4-biphenylacetic acid, 4-acridine 4β-D-glucuronide, N-acetyl leukotriene E4, 17β-oestradiol 3β-D-glucuronide and taurolithocholate 3-sulphate. Inside-out vesicles from human erythrocytes contain a comparable ATP-dependent transport system. These results show that NAc-DNP-Cys and naphthyl glucuronide are high-affinity substrates for a single system identified previously as a low-affinity transporter of DNP-SG. Substrate and inhibitor studies identify this system as a novel multispecific organic-anion transport system (MOAT4) that accommodates glucuronides and mercapturates and is distinct from other MOAT transporters. Human erythrocytes contain an additional ATP-dependent system for NAc-DNP-Cys (Km 33 µM) that does not transport monoglucuronides.

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.

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