scholarly journals Mutations in Novel Organic Cation Transporter (OCTN2), an Organic Cation/Carnitine Transporter, with Differential Effects on the Organic Cation Transport Function and the Carnitine Transport Function

1999 ◽  
Vol 274 (47) ◽  
pp. 33388-33392 ◽  
Author(s):  
Pankaj Seth ◽  
Xiang Wu ◽  
Wei Huang ◽  
Frederick H. Leibach ◽  
Vadivel Ganapathy
Keyword(s):  
Organic Cation ◽  
Organic Cation Transporter ◽  
Cation Transport ◽  
Organic Cation Transport ◽  
Transport Function ◽  
Differential Effects ◽  
Carnitine Transporter ◽  
Carnitine Transport

Peritubular organic cation transport in isolated rabbit proximal tubules

1994 ◽  
Vol 266 (3) ◽  
pp. F450-F458 ◽  
Author(s):  
C. E. Groves ◽  
K. K. Evans ◽  
W. H. Dantzler ◽  
S. H. Wright
Keyword(s):  
Organic Cation ◽  
High Capacity ◽  
Organic Cation Transporter ◽  
Cation Transport ◽  
Proximal Tubules ◽  
Organic Cation Transport ◽  
Inhibitory Potency ◽  
Renal Proximal Tubules ◽  
Michaelis Constants ◽  
Maximal Capacity

The physiological characteristics of peritubular organic cation transport were examined by measuring the transport of the organic cation tetraethylammonium (TEA) in rabbit renal proximal tubule suspensions and isolated nonperfused rabbit renal proximal tubules. Peritubular organic cation transport in both single S2 segments and suspensions of isolated renal proximal tubules was found to be a high-capacity, high-affinity, carrier-mediated process. For tubule suspensions, the maximal capacity of the carrier for TEA (Jmax) and the concentration of TEA at 1/2 Jmax (Kt) (1.49 +/- 0.21 nmol.min-1.mg dry wt-1 and 131 +/- 16 microM, respectively), did not differ significantly from those measured in single S2 segments (Jmax, 1.16 +/- 0.075 nmol.min-1.mg dry wt-1; Kt, 108 +/- 10 microM). In addition, the pattern of inhibition of peritubular TEA transport by long-chain n-tetraalkylammonium compounds (n = 1-5) was both qualitatively and quantitatively similar in single S2 segments and tubule suspensions, exhibiting an increase in inhibitory potency with increasing alkyl chain length. For example, in tubule suspensions, apparent Michaelis constants for inhibition of TEA uptake ranged from 1.3 mM for tetramethylammonium (TMA) to 0.8 microM for tetrapentylammonium (TPeA). To determine whether these compounds were substrates for the peritubular organic cation transporter, their effect on the efflux of [14C]TEA from tubule suspensions was examined. A concentration of 0.5 mM of the short-chain tetraalkyls TMA or TEA increased the efflux of [14C]TEA (i.e., trans-stimulated) from tubules in suspension. The longer-chain tetraalkyls tetrapropylammonium, tetrabutylammonium, and TPeA all decreased the efflux of [14C]TEA from tubules in suspension; TPeA completely blocked efflux.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Carnitine/organic cation transporter OCTN2-mediated transport of carnitine in primary-cultured epididymal epithelial cells

Reproduction ◽  
2005 ◽  
Vol 130 (6) ◽  
pp. 931-937 ◽  
Author(s):  
Daisuke Kobayashi ◽  
Masanori Irokawa ◽  
Tomoji Maeda ◽  
Akira Tsuji ◽  
Ikumi Tamai
Keyword(s):  
Epithelial Cells ◽  
Organic Cation ◽  
Basolateral Membrane ◽  
Organic Cation Transporter ◽  
Systemic Circulation ◽  
Transport Systems ◽  
Pcr Analysis ◽  
Carnitine Transporter ◽  
Carnitine Transport ◽  
Cationic Compounds

Carnitine is essential for the acquisition of motility and maturation of spermatozoa in the epididymis, and is accumulated in epididymal fluid. In this study, carnitine transport into primary-cultured rat epididymal epithelial cells was characterized to clarify the nature of the transporter molecules involved. Uptake of carnitine by primary-cultured epididymal epithelial cells was time, Na+and concentration dependent. Kinetic analysis of carnitine uptake by the cells revealed the involvement of high- and low-affinity transport systems withKm values of 21 μM and 2.2 mM respectively. The uptake of carnitine by the cells was significantly reduced by inhibitors of carnitine/organic cation transporter (OCTN2), such as carnitine analogues and cationic compounds. In RT-PCR analysis, OCTN2 expression was detected. These results demonstrated that the high-affinity carnitine transporter OCTN2, which is localized at the basolateral membrane of epididymal epithelial cells, mediates carnitine supply into those cells from the systemic circulation as the first step of permeation from blood to spermatozoa.

Molecular cloning of rabbit organic cation transporter rbOCT2 and functional comparisons with rbOCT1

2002 ◽  
Vol 283 (1) ◽  
pp. F124-F133 ◽  
Author(s):  
Xiaohong Zhang ◽  
Kristen K. Evans ◽  
Stephen H. Wright
Keyword(s):  
Proximal Tubule ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Cation Transport ◽  
Rabbit Kidney ◽  
Organic Cation Transport ◽  
Major Contributor ◽  
Organic Cation Transporters ◽  
Functional Roles ◽  
Cation Uptake

Multiple organic cation transporters (OCTs) are present in rabbit kidney and may play different functional roles. We cloned rabbit OCT2 (rbOCT2) and compared its function with that of rabbit OCT1 (rbOCT1). In transiently transfected COS-7 cells, rbOCT1 and rbOCT2 mediated uptake of [3H]tetraethylammonium (TEA) with Ktvalues of 188 and 125 μM, respectively. n-Tetraalkylammonium compounds showed similar affinities for the two homologs, with IC50values for inhibition of OCT1- and OCT2-mediated [3H]TEA transport, respectively, of 4,538 and 1,395 μM for tetramethylammonium, 88.5 and 3.9 μM for tetrapropylammonium, 13.9 and 5.3 μM for tetrabutylammonium, and 8.8 and 7.6 μM for tetrapentylammonium. However, the transporters had very different affinities for cimetidine (CIM): IC50of 916 and 5.7 μM for rbOCT1 and rbOCT2, respectively. CIM inhibition of TEA uptake into single S2 segments of rabbit proximal tubule was used to estimate the contributions of OCT1 and OCT2 to basolateral organic cation uptake. The median IC50for CIM inhibition of TEA uptake was 12.3 μM, suggesting that OCT2 is the major contributor to basolateral organic cation transport in the S2 segment of proximal tubule in rabbit kidney.

scholarly journals Expression of renal organic cation transporter in Xenopus laevis oocytes

1992 ◽  
Vol 283 (2) ◽  
pp. 409-411 ◽  
Author(s):  
R Hori ◽  
M Hirai ◽  
T Katsura ◽  
M Takano ◽  
M Yasuhara ◽  
...  
Keyword(s):  
Xenopus Laevis ◽  
Transport System ◽  
Organic Cation ◽  
Expression System ◽  
Fold Increase ◽  
Organic Cation Transporter ◽  
Sucrose Density Gradient ◽  
Cation Transport ◽  
Organic Cation Transport ◽  
Xenopus Laevis Oocytes

The expression of the organic cation transport system of rat renal proximal tubules has been studied in Xenopus laevis oocytes injected with poly(A)+ RNA from the rat renal cortex. The effectiveness of the technique was confirmed by examining expression of the Na+/D-glucose co-transporter. Compared with water-injected and non-injected oocytes, the injection of total poly(A)+ RNA resulted in about a 3-fold increase in tetraethylammonium (TEA) uptake activity. TEA uptake by poly(A)(+)-RNA-injected oocytes was time-dependent and was inhibited by cimetidine and HgCl2, but not by p-aminohippurate. After size-fractionation on a sucrose density gradient, a 1.4-2.4 kb poly(A)+ RNA fragment was identified that expressed the organic cation transport system in oocytes. These results demonstrate that the renal organic cation transporter was expressed in oocytes and that this expression system can provide an effective assay procedure for cloning of the organic cation transporter.

Functional Impairment of Renal Organic Cation Transport in Experimental Diabetes

2002 ◽  
Vol 90 (4) ◽  
pp. 181-186 ◽  
Author(s):  
Brett Grover ◽  
Christopher Auberger ◽  
Rangaprasad Sarangarajan ◽  
William Cacini
Keyword(s):  
Functional Impairment ◽  
Organic Cation ◽  
Experimental Diabetes ◽  
Cation Transport ◽  
Organic Cation Transport

In Vitro and In Vivo Evaluation of Amphiphilic Chitosan Derivatives for Inhibition of Organic Cation Transport Function

2020 ◽  
Vol 859 ◽  
pp. 45-50
Author(s):  
Sirima Soodvilai ◽  
Sunhapas Soodvila ◽  
Warayuth Sajomsang ◽  
Theerasak Rojanarata ◽  
Prasopchai Patrojanasophon ◽  
...  
Keyword(s):  
Organic Cation ◽  
Drug Disposition ◽  
Organic Cation Transporter ◽  
Transport Function ◽  
Chitosan Derivatives ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
Renal Proximal Tubular

This study explored the interaction of amphiphilic chitosan derivatives, N-benzyl-N,O-succinyl chitosan (BSCS), N-naphthyl-N,O-succinyl chitosan (NSCS) and N-octyl-N,O-succinyl chitosan (OSCS), with renal organic cation transporter 2 (OCT2). The influence of amphiphilic chitosan derivatives on renal OCT2 transport function was determined by monitoring the transport of a positively charged substrate into human renal proximal tubular epithelial cells (RPTEC/TERT1 cells), and murine kidney. Amphiphilic chitosan derivatives inhibited 3H-MPP (a substrate of OCT2) transport in the renal cells in a concentration-reliance characteristic. OSCS reduced the accumulation of the cationic drug, cisplatin, in RPTEC/TERT1 cells. This effect was more pronounced than that of other chitosan derivatives. In addition, co-administration of cisplatin and OSCS significantly reduced cisplatin accumulation compared with receiving cisplatin alone. This result was accompanied by the decrease in nephrotoxicity induced by cisplatin. In conclusion, OSCS inhibited OCT2 function and reduced cationic drug disposition in human renal proximal tubular cells and murine kidney.

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