AJP - Renal Physiology, Vol 252, Issue 3 525-F535, Copyright © 1987 by American Physiological Society

ARTICLES

Cimetidine transport in rabbit renal cortical brush-border membrane vesicles

T. D. McKinney and M. E. Kunnemann

Cimetidine is an organic cation and commonly prescribed drug that is eliminated primarily by proximal renal tubular secretion. The present studies evaluated cimetidine transport in rabbit renal cortical brush-border membrane vesicles (BBMV). [3H]Cimetidine uptake varied inversely with media osmolarity and was stimulated with uphill transport above equilibrium values (overshoot) produced by an initial proton gradient directed from the vesicle interior outwardly. Uphill transport occurred earlier and was of greater magnitude at 25 degrees C than at 5 degrees C. pH-stimulated [3H]cimetidine uptake was inhibited by excess nonradiolabeled cimetidine, quinidine, and procainamide but was affected little by probenecid. Tetraethylammonium inhibited cimetidine uptake in the presence and absence of an initial proton gradient, indicating that nonionic diffusion and simple diffusion cannot totally account for cimetidine transport in BBMV. The protonophore carbonyl cyanide trifluoromethoxyphenylhydrazone (FCCP) inhibited pH-stimulated cimetidine uptake but had no effect on uptake occurring in the absence of an initial pH gradient. Preloading BBMV with an excess of procainamide enhanced cimetidine uptake. However, in the presence of FCCP, the combination of FCCP and valinomycin, or nigericin the effect of preloading with procainamide was diminished, suggesting that the apparent countertransport of cimetidine produced by procainamide was indirect and due to generation of a transvesicular proton gradient. These results are consistent with the hypothesis that cimetidine is transported across BBMV by organic cation-proton exchange.

This article has been cited by other articles:

				X. Zhang, N. J. Cherrington, and S. H. Wright Molecular identification and functional characterization of rabbit MATE1 and MATE2-K Am J Physiol Renal Physiol, July 1, 2007; 293(1): F360 - F370. [Abstract] [Full Text] [PDF]

				M. Tsuda, T. Terada, J.-i. Asaka, M. Ueba, T. Katsura, and K.-i. Inui Oppositely directed H+ gradient functions as a driving force of rat H+/organic cation antiporter MATE1 Am J Physiol Renal Physiol, February 1, 2007; 292(2): F593 - F598. [Abstract] [Full Text] [PDF]

				S. H. Wright and W. H. Dantzler Molecular and Cellular Physiology of Renal Organic Cation and Anion Transport Physiol Rev, July 1, 2004; 84(3): 987 - 1049. [Abstract] [Full Text] [PDF]

				H. Mizuuchi, T. Katsura, H. Saito, Y. Hashimoto, and K.-I. Inui Transport Characteristics of Diphenhydramine in Human Intestinal Epithelial Caco-2 Cells: Contribution of pH-Dependent Transport System J. Pharmacol. Exp. Ther., July 1, 1999; 290(1): 388 - 392. [Abstract] [Full Text]

				N. Piyapolrungroj, C. Li, R. L. Pisoni, and D. Fleisher Cimetidine Transport in Brush-Border Membrane Vesicles from Rat Small Intestine J. Pharmacol. Exp. Ther., April 1, 1999; 289(1): 346 - 353. [Abstract] [Full Text]

				L. Zhang, M. J. Dresser, J. K. Chun, P. C. Babbitt, and K. M. Giacomini Cloning and Functional Characterization of a Rat Renal Organic Cation Transporter Isoform (rOCT1A) J. Biol. Chem., June 27, 1997; 272(26): 16548 - 16554. [Abstract] [Full Text] [PDF]