caa a22 4500 477126359 CHVBK 20180405111650.0 cr unu---uuuuu 170330e19970701xx s 000 0 eng 10.1023/A:1012164203648 doi (NATIONALLICENCE)springer-10.1023/A:1012164203648 Characterization of Guanidine Transport in Human Renal Brush Border Membranes [Elektronische Daten] [Joanne Chun, Lei Zhang, Micheline Piquette-Miller, Ernest Lau, Li-Qin Tong, Kathleen Giacomini] Purpose. 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 μM) 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. Plenum Publishing Corporation, 1997 brush-border membrane vesicles nationallicence organic cation transport nationallicence tetraethylammonium nationallicence guanidine nationallicence human kidney nationallicence transporters nationallicence Chun Joanne Department of Biopharmaceutical Sciences, University of California, San Francisco, 94143, San Francisco, California aut Zhang Lei Department of Biopharmaceutical Sciences, University of California, San Francisco, 94143, San Francisco, California aut Piquette-Miller Micheline Faculty of Pharmacy, University of Toronto, M5S 2S2, Toronto, Ontario, Canada aut Lau Ernest aut Tong Li-Qin Department of Biopharmaceutical Sciences, University of California, San Francisco, 94143, San Francisco, California aut Giacomini Kathleen Department of Biopharmaceutical Sciences, University of California, San Francisco, 94143, San Francisco, California aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/7(1997-07-01), 936-941 0724-8741 14:7<936 1997 14 11095 https://doi.org/10.1023/A:1012164203648 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012164203648 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chun Joanne Department of Biopharmaceutical Sciences, University of California, San Francisco, 94143, San Francisco, California aut NATIONALLICENCE 700 1- Zhang Lei Department of Biopharmaceutical Sciences, University of California, San Francisco, 94143, San Francisco, California aut NATIONALLICENCE 700 1- Piquette-Miller Micheline Faculty of Pharmacy, University of Toronto, M5S 2S2, Toronto, Ontario, Canada aut NATIONALLICENCE 700 1- Lau Ernest aut NATIONALLICENCE 700 1- Tong Li-Qin Department of Biopharmaceutical Sciences, University of California, San Francisco, 94143, San Francisco, California aut NATIONALLICENCE 700 1- Giacomini Kathleen Department of Biopharmaceutical Sciences, University of California, San Francisco, 94143, San Francisco, California aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/7(1997-07-01), 936-941 0724-8741 14:7<936 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer