Distinct characteristics of organic cation transporters, OCT1 and OCT2, inthe basolateral membrane of renal tubules

Purpose. This study was performed to determine the detailed mRNA distributi on of organic cation transporters, rOCT1 and rOCT2, along the rat nephron a nd to distinguish the substrate affinities of these transporters. Methods. The distributions of rOCT1 and rOCT2 mRNA were determined by rever se transcriptase polymerase chain reaction analysis of microdissected nephr on segments. Using MDCK cells transfected with rOCT1 or rOCT2 cDNA, the inh ibitory effects of various compounds on the uptake of [C-14]tetraethylammon ium were assessed. Results. rOCT1 mRNA was detected primarily in the superficial and juxtamedu llary proximal convoluted tubules, whereas rOCT2 mRNA was detected widely i n the superficial and juxtamedullary proximal straight and convoluted tubul es, medullary thick ascending limbs, distal convoluted tubule, and cortical collecting duct. The IC50 values for cationic, drugs and endogenous cation s on [C-14]tetraethylammonium uptake across the basolateral membranes in th e transfectants indicated that rOCT1 and rOCT2 had similar inhibitor specif icity for many compounds but showed moderate differences in the specificity for several compounds, such as 1-methyl-4-phenylpyridinium, dopamine, diso pyramide, and chlorpheniramine. Conclusions. rOCT1 and rOCT2 possess similar but not identical multispecifi cities for various compounds with distinct distributions along the nephron, indicating that the two transporters share physiologic and pharmacologic r oles in the renal handling of cationic compounds.