cDNA Sequence, Transport Function, and Genomic Organization of Human OCTN2, a New Member of the Organic Cation Transporter Family

1998 ◽  
Vol 246 (3) ◽  
pp. 589-595 ◽  
Author(s):  
Xiang Wu ◽  
Puttur D. Prasad ◽  
Frederick H. Leibach ◽  
Vadivel Ganapathy
Keyword(s):  
Cdna Sequence ◽  
Organic Cation ◽  
Genomic Organization ◽  
Organic Cation Transporter ◽  
Transport Function ◽  
Transporter Family

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.

scholarly journals Molecular Cloning and Characterization of NKT, a Gene Product Related to the Organic Cation Transporter Family That Is Almost Exclusively Expressed in the Kidney

1997 ◽  
Vol 272 (10) ◽  
pp. 6471-6478 ◽  
Author(s):  
Carlos E. Lopez-Nieto ◽  
Guofeng You ◽  
Kevin T. Bush ◽  
Elvino J. G. Barros ◽  
Davio R. Beier ◽  
...  
Keyword(s):  
Molecular Cloning ◽  
Gene Product ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Transporter Family

scholarly journals MOLECULAR AND FUNCTIONAL IDENTIFICATION OF NOVEL HUMAN ORGANIC CATION TRANSPORTER FAMILY, OCTN1 AND OCTN2

1998 ◽  
Vol 13 (supplement) ◽  
pp. 106-107
Author(s):  
Hikaru YABUUCHI ◽  
Rikiya OHASHI ◽  
Kazuki SAKAMOTO ◽  
Jun-ichi NEZU ◽  
Asuka OKU ◽  
...  
Keyword(s):  
Organic Cation ◽  
Organic Cation Transporter ◽  
Functional Identification ◽  
Transporter Family

Functional and pharmacological characterization of human Na+-carnitine cotransporter hOCTN2

2000 ◽  
Vol 279 (3) ◽  
pp. F584-F591 ◽  
Author(s):  
Carsten A. Wagner ◽  
Ulrike Lükewille ◽  
Simone Kaltenbach ◽  
Ivano Moschen ◽  
Angelika Bröer ◽  
...  
Keyword(s):  
Organic Cation ◽  
Organic Cation Transporter ◽  
Carnitine Deficiency ◽  
Significant Inhibition ◽  
Xenopus Laevis Oocytes ◽  
Channel Blockers ◽  
Pharmacological Characterization ◽  
Transporter Family ◽  
Carnitine Transport ◽  
Induced Currents

l-Carnitine is essential for the translocation of acyl-carnitine into the mitochondria for β-oxidation of long-chain fatty acids. It is taken up into the cells by the recently cloned Na+-driven carnitine organic cation transporter OCTN2. Here we expressed hOCTN2 in Xenopus laevis oocytes and investigated with two-electrode voltage- clamp and flux measurements its functional and pharmacological properties as a Na+-carnitine cotransporter. l-carnitine transport was electrogenic. The l-carnitine-induced currents were voltage and Na+ dependent, with half-maximal currents at 0.3 ± 0.1 mM Na+ at −60 mV. Furthermore,l-carnitine-induced currents were pH dependent, decreasing with acidification. In contrast to other members of the organic cation transporter family, hOCTN2 functions as a Na+-coupled carnitine transporter. Carnitine transport was stereoselective, with an apparent Michaelis-Menten constant ( K m) of 4.8 ± 0.3 μM for l-carnitine and 98.3 ± 38.0 μM for d-carnitine. The substrate specificity of hOCTN2 differs from rOCT-1 and hOCT-2 as hOCTN2 showed only small currents with classic OCT substrates such as choline or tetraethylammonium; by contrast hOCTN2 mediated transport of betaine. hOCTN2 was inhibited by several drugs known to induce secondary carnitine deficiency. Most potent blockers were the antibiotic emetine and the ion channel blockers quinidine and verapamil. The apparent IC50 for emetine was 4.2 ± 1.2 μM. The anticonvulsant valproic acid did not induce a significant inhibition of carnitine transport, pointing to a different mode of action. In summary, hOCTN2 mediates electrogenic Na+-dependent stereoselective high-affinity transport ofl-carnitine and Na+. hOCTN2 displays transport properties distinct from other members of the OCT family and is directly inhibited by several substances known to induce systemic carnitine deficiency.

Sign in / Sign up

Export Citation Format

Share Document