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OBJECTIVE Organic cation transporters in the renal proximal tubule are important in the secretion of many clinically used drugs and their metabolites. The goal of this study was to determine the mechanisms of guanidine transport in human kidney. METHODS Brush-border membrane vesicles were prepared from donor human kidneys deemed unsuitable for renal transplantation. RESULTS Uptake of [14C]-guanidine (50 microM) in the vesicles, as determined by rapid filtration, was significantly greater in the presence of an outwardly-directed proton gradient, at all early time points, than in the absence of the gradient. Proton-stimulated uptake of [14C]-guanidine at 30 sec (32.0 +/- 1.24 pmol/mg protein) was significantly inhibited by a number of organic cations including 5 mM unlabeled guanidine (14.8 +/- 1.84 pmol/mg protein) and 5 mM MIBA (9.14 +/- 3.80 pmol/ mg protein), but not by 5 mM TEA (28.4 +/- 5.67 pmol/mg protein). Guanidine, but not TEA, trans-stimulated [14C]-guanidine uptake. Conversely, TEA, but not guanidine, trans-stimulated [14C]-TEA uptake in the vesicles. The proton-dependent transport of guanidine was characterized by a Km of 3.52 +/- 0.42 mM (SE) and a Vmax of 34.6 +/- 8.64 pmol/mg protein/sec (SE). CONCLUSIONS These results demonstrate that guanidine transport in human renal brush border membrane vesicles is stimulated by a proton gradient. Evidence was obtained suggesting that the transporter for guanidine is distinct from the previously described organic cation proton antiporter for TEA.
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