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Tubular absorption and urinary secretion are important physiological functions for the maintenance of body fluid homeostasis and detoxification of drugs and xenobiotics. The proximal tubular epithelial cells play a principal role in limiting or preventing the toxicity of administered drugs by actively secreting organic cations from the circulation into the urine. Rat (r) OCT2 was identified as a second member of the organic cation transporter (OCT) family and is predominantly expressed in the kidney. In the reverse-transcriptase-polymerase chain reaction of microdissected nephron segments, 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 tubules and some other nephron segments. The inhibitory potencies of cationic drugs and endogenous cations on the tetraethylammoniun (TEA) uptake via rOCT1 and rOCT2 indicates that rOCT1 and rOCT2 have similar affinity for many compounds, although there are moderate differences in the affinity for several compounds, such as 1-methyl-4-phenyl-pyridinium, dopamine, disopyramide, and chlorpheniramine. On the other hand, there were gender differences in the expression levels of rOCT2, but not of rOCT1, in rat kidneys; both mRNA and protein levels of rOCT2 in the kidneys were higher in males than females. These results suggest that rOCT1 and rOCT2 play distinct roles in the basolateral membranes of renal tubules mediating tubular secretion of cationic drugs.

Molecular Diversity of Organic Cation Transporter (OCT) Mediating Renal Excretion of Drugs.