Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney.
We examined in this study the expression of the potential-sensitive organic cation transporter OCT3 in the kidney. A functionally active OCT3 was cloned from a mouse kidney cDNA library. The cloned transporter was found to be capable of mediating potential-dependent transport of a variety of organic cations including tetraethylammonium. This function was confirmed in two different heterologous expression systems involving mammalian cells and Xenopus laevis oocytes. We have also isolated the mouse OCT3 gene and deduced its structure and organization. The OCT3 gene consists of 11 exons and 10 introns. In situ hybridization studies in the mouse kidney have shown that OCT3 mRNA is expressed primarily in the cortex. The expression is evident in the proximal and distal convoluted tubules. The expression of OCT3 in human kidney was confirmed by RT-PCR. We have also cloned OCT3 from human placenta and human kidney. Human OCT3 exhibits 86% identity with mouse OCT3 in amino acid sequence. Human OCT3 was found to transport tetraethylammonium and a variety of other organic cations. The transport process was electrogenic. We conclude that OCT3 is expressed in mammalian kidney and that it plays an important role in the renal clearance of cationic drugs.
Wu
X
X
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia 30912, USA.
Huang
W
W
Ganapathy
M E
ME
Wang
H
H
Kekuda
R
R
Conway
S J
SJ
Leibach
F H
FH
Ganapathy
V
V
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D002250:Carbon Radioisotopes; D002412:Cations / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D005091:Exons; D005786:Gene Expression Regulation / Q000502:physiology; D006367:HeLa Cells; D006540:Herbicides / Q000494:pharmacology; D006801:Humans; D017403:In Situ Hybridization; D007438:Introns; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D050814:Octamer Transcription Factor-3; D009865:Oocytes / Q000502:physiology; D010857:Pigment Epithelium of Eye / Q000166:cytology; D012333:RNA, Messenger / Q000032:analysis; D019789:Tetraethylammonium / Q000493:pharmacokinetics; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D014316:Tritium; D014982:Xenopus laevis
D002250:Carbon Radioisotopes; D002412:Cations; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D015259:Dopamine Agents; D006540:Herbicides; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C494174:Pou5f1 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D014316:Tritium; D009536:Niacinamide; C039465:5-dimethylamiloride; D019789:Tetraethylammonium; D000584:Amiloride; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; C008472:N-methylnicotinamide