Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules.
OBJECTIVE
This study was performed to determine the detailed mRNA distribution of organic cation transporters, rOCT1 and rOCT2, along the rat nephron and to distinguish the substrate affinities of these transporters.


METHODS
The distributions of rOCT1 and rOCT2 mRNA were determined by reverse transcriptase polymerase chain reaction analysis of microdissected nephron segments. Using MDCK cells transfected with rOCT1 or rOCT2 cDNA, the inhibitory effects of various compounds on the uptake of [14C]tetraethylammonium were assessed.


RESULTS
rOCT1 mRNA was detected primarily in the superficial and juxtamedullary proximal convoluted tubules, whereas rOCT2 mRNA was detected widely in the superficial and juxtamedullary proximal straight and convoluted tubules, medullary thick ascending limbs, distal convoluted tubule, and cortical collecting duct. The IC50 values for cationic drugs and endogenous cations on [14C]tetraethylammonium uptake across the basolateral membranes in the transfectants indicated that rOCT1 and rOCT2 had similar inhibitor specificity for many compounds but showed moderate differences in the specificity for several compounds, such as 1-methyl-4-phenylpyridinium, dopamine, disopyramide, and chlorpheniramine.


CONCLUSIONS
rOCT1 and rOCT2 possess similar but not identical multispecificities for various compounds with distinct distributions along the nephron, indicating that the two transporters share physiologic and pharmacologic roles in the renal handling of cationic compounds.
Urakami
Y
Y
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
Okuda
M
M
Masuda
S
S
Akazawa
M
M
Saito
H
H
Inui
K
K
D000818:Animals; D002460:Cell Line; D004285:Dogs; D007668:Kidney / Q000378:metabolism; D007684:Kidney Tubules / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008566:Membranes / Q000737:chemistry / Q000378:metabolism; D009399:Nephrons / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000737:chemistry*; D027702:Organic Cation Transporter 1 / Q000737:chemistry*; D000075102:Organic Cation Transporter 2; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011994:Recombinant Proteins / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013379:Substrate Specificity; D019789:Tetraethylammonium / Q000378:metabolism; D014162:Transfection
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; D019789:Tetraethylammonium