cDNA cloning and functional expression of a novel rat kidney organic cation transporter, OCT2.
A cDNA encoding a novel organic cation transporter, designated as OCT2 was isolated from the rat kidney. The rat OCT2 cDNA (2,205 bp) had an open reading frame encoding for a 593-amino acid protein (calculated molecular mass of 66 kDa) which shows 67% identity with the rat OCT1. Northern hybridization and reverse transcription-PCR analyses revealed that the rat OCT2 mRNA transcript was expressed predominantly in the kidney, at higher level in the medulla than in the cortex, but this transcript was not detected in the brain, heart, lung, liver, small intestine or spleen. When expressed in Xenopus oocytes, rat OCT2 stimulated the uptake of tetraethylammonium, and the uptake was markedly inhibited by the presence of cimetidine, procainamide and quinidine. These findings suggest that OCT2 is responsible for the transport of cationic drugs in the kidney.
Okuda
M
M
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
Saito
H
H
Urakami
Y
Y
Takano
M
M
Inui
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport / Q000187:drug effects; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism; D002927:Cimetidine / Q000494:pharmacology; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary; D005260:Female; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D000075102:Organic Cation Transporter 2; D016133:Polymerase Chain Reaction; D011342:Procainamide / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000378:metabolism; D014982:Xenopus laevis
D002352:Carrier Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D008565:Membrane Proteins; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D000075102:Organic Cation Transporter 2; D012333:RNA, Messenger; D011994:Recombinant Proteins; C100590:Slc22a2 protein, rat; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D002927:Cimetidine; D011802:Quinidine; D011342:Procainamide