Carrier-mediated transport systems of tetraethylammonium in rat renal brush-border and basolateral membrane vesicles

Takano, Mikihisa; Inui, Ken Ichi; Okano, Toshio; Saya, Hideyuki; Hori, Ryohei

doi:10.1016/0005-2736(84)90556-x

Cited by 158 publications

(87 citation statements)

References 21 publications

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“…Using tetraethylammonium (TEA), as a probe of organic cation secretion across the apical membrane, an electroneutral organic cation/proton antiport (OC/H+) in which exit of organic cations across the apical membrane is tightly coupled to the entry of protons has been widely documented (Pritchard & Miller, 1993). Indeed both proton-gradient driven uptake of TEA and its converse organic cation-gradient driven proton flux have now been demonstrated in isolated membrane vesicles (Holohan & Ross, 1981;Takano et al, 1983;Hsyu et al, 1987;Solkol et al, 1988;Ott et al, 1991) and cultured renal epithelial cell lines (Innui et al, 1985;Yuan et al, 1991;Saito et al, 1992). Indirect evidence suggests that in addition to TEA, OC/H' antiport accepts a wide range of substrates, many of which are weak bases (McKinney & Speeg, 1982;McKinney & Kunneman, 1985;Boom et al, 1992;Takano et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

pH‐dependent transport of procainamide in cultured renal epithelial monolayers of OK cells: consistent with nonionic diffusion

Dudley

Brown

1995

British J Pharmacology

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1 Previous studies suggest that procainamide is a substrate for organic cation/proton antiport. In order to study the coupling between procainamide flux and proton flux in greater detail we investigated the effects of extracellular procainamide addition upon intracellular pH in cultured monolayers of renal 5 Procainamide efflux from procainamide-loaded cell monolayers resulted in a significant acidification of intracellular pH. As with procainamide uptake, this result could be ascribed to the movement of neutral weak base. 6 These effects of procainamide upon intracellular pH are consistent with nonionic diffusion of procainamide rather than an interaction of procainamide with the organic cation/proton antiporter. In addition, the results suggest that organic cation/proton antiport is not highly expressed in OK cells.

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Section: Introductionmentioning

confidence: 99%

pH‐dependent transport of procainamide in cultured renal epithelial monolayers of OK cells: consistent with nonionic diffusion

Dudley

Brown

1995

British J Pharmacology

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“…The H ϩ /organic cation antiporter in renal brush-border membranes mediates active extrusion of cationic drugs or toxins out of renal tubular cells (Ullrich, 1997). The oppositely directed H ϩ gradient was demonstrated to be a driving force for the transport of organic cations such as TEA, a prototype substrate (Takano et al, 1984). More recently, the apical type of H ϩ /organic cation antiporter, rat multidrug and toxin extrusion 1 (rMATE1/Slc47a1), has been identified and functionally characterized (Ohta et al, 2006;Terada et al, 2006).…”

mentioning

confidence: 99%

Altered Pharmacokinetics of Cationic Drugs Caused by Down-Regulation of Renal Rat Organic Cation Transporter 2 (Slc22a2) and Rat Multidrug and Toxin Extrusion 1 (Slc47a1) in Ischemia/Reperfusion-Induced Acute Kidney Injury

Matsuzaki

Morisaki²,

Sugimoto³

et al. 2008

Drug Metab Dispos

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ABSTRACT:In the proximal tubules of rat (r) kidney, the polyspecific organic cation transporters (OCTs), rOCT1 and rOCT2, mediate the basolateral uptake of various organic cations, including many drugs, toxins, and endogenous compounds, and the apical type of H ؉ / organic cation antiporter, rat multidrug and toxin extrusion 1 (rMATE1), mediate the efflux of organic cations. Renal clearances of H 2 receptor antagonists, including famotidine, were reported to be decreased in patients with kidney disease. Therefore, acute kidney injury (AKI) could influence renal excretion and disposition of organic cations accompanied by the regulation of organic cation transporters. The aim of this study was to investigate the pharmacokinetic alteration of cationic drugs and the expression of tubular organic cation transporters, rOCT1, rOCT2, and rMATE1, in ischemia/reperfusion (I/R)-induced AKI rats. I/R-induced AKI increased the plasma concentration of i.v. administrated famotidine, a substrate for rOCT1 and rOCT2, or tetraethylammonium (TEA), a substrate for rOCT1, rOCT2, and rMATE1. The areas under the plasma concentration curves for famotidine and TEA were 2-and 6-fold higher in I/R rats than in sham-operated rats, respectively. The accumulation of TEA into renal slices was significantly decreased, suggesting that organic cation transport activity at the basolateral membranes was reduced in I/R rat kidney. The protein expressions of basolateral rOCT2 and luminal rMATE1 were down-regulated in I/R rat kidneys. These data suggest that the urinary secretion of cationic drugs via epithelial organic cation transporters is decreased in AKI.

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“…Transepithelial transport of TEA from the basolateral side is potently inhibited by decynium22, applied to the apical side, whereas application to the basolateral side has no effect (15). Moreover, apical membrane vesicles from LLC-PK 1 cells contain, analogous to renal brush-border membrane vesicles from various species (27)(28)(29)(30)(31)(32), an organic cation uptake mechanism that markedly depends on pH (33). Together, these findings strongly suggest that LLC-PK 1 cells express the apical type of organic cation transporter.…”

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confidence: 99%

Primary Structure and Functional Expression of the Apical Organic Cation Transporter from Kidney Epithelial LLC-PK1Cells

Gründemann

Babin‐Ebell²,

Martel³

et al. 1997

Journal of Biological Chemistry

175

145

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14 C]TEA uptake into LLC-PK 1 cells and 293 cells transfected with OCT2p (r ‫؍‬ 0.995; p < 0.001; n ‫؍‬ 6). Although OCT2p is structurally related to OCT1r, the basolateral organic cation transporter from rat kidney, the transporters could be clearly discriminated pharmacologically with corticosterone, decynium22, and O-methylisoprenaline. The findings at hand suggest that OCT2 corresponds to the apical type of organic cation transporter. Reverse transcriptase-polymerase chain reaction indicates that mRNA of OCT1r is limited to non-neuronal tissue, whereas OCT2r, the OCT2p homologue from rat, was found in both the kidney and central nervous regions known to be rich in the monoamine transmitter dopamine.

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Carrier-mediated transport systems of tetraethylammonium in rat renal brush-border and basolateral membrane vesicles

Cited by 158 publications

References 21 publications

pH‐dependent transport of procainamide in cultured renal epithelial monolayers of OK cells: consistent with nonionic diffusion

pH‐dependent transport of procainamide in cultured renal epithelial monolayers of OK cells: consistent with nonionic diffusion

Altered Pharmacokinetics of Cationic Drugs Caused by Down-Regulation of Renal Rat Organic Cation Transporter 2 (Slc22a2) and Rat Multidrug and Toxin Extrusion 1 (Slc47a1) in Ischemia/Reperfusion-Induced Acute Kidney Injury

Primary Structure and Functional Expression of the Apical Organic Cation Transporter from Kidney Epithelial LLC-PK1Cells

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