AJP - Renal Physiology, Vol 254, Issue 1 56-F61, Copyright © 1988 by American Physiological Society

ARTICLES

Interactions of organic anions with the organic cation transporter in renal BBMV

P. H. Hsyu, L. G. Gisclon, A. C. Hui and K. M. Giacomini
School of Pharmacy, University of California, San Francisco 94143.

It is generally assumed that the organic cation transport system in the renal proximal tubule is specific for organic cations and the transport of organic cations is not affected by organic anions. However, there are also data in the literature demonstrating that probenecid, a classical inhibitor of organic anion transport systems, inhibits the transport of an organic cation, cimetidine, in the renal proximal tubule. In this study we investigated the effects of probenecid and furosemide on the transport of N'-methylnicotinamide (NMN) the classical substrate of the organic cation transporter, in brush-border membrane vesicles prepared from rabbit renal cortex. In the presence of a pH gradient, both probenecid (10 mM) and furosemide reduced the initial uptake of NMN. Probenecid reduced the initial uptake of NMN to 12.1% of the control values (1.19 +/- 0.26 pmol/mg) and furosemide reduced the initial uptake of NMN to 39.2%. Probenecid (10 mM) also decreased the initial transport of NMN in the absence of a pH gradient. Inhibition of the transport of NMN by probenecid was concentration dependent, with the concentration of probenecid resulting in 50% inhibition of the transport of NMN equal to 2.31 +/- 1.18 mM in the presence of a pH gradient. Probenecid appeared to be a competitive inhibitor of NMN transport. The apparent Km (mean +/- SE) of NMN transport (2.01 +/- 0.78 mM) was increased to 18.7 +/- 10 mM (P less than 0.05) by probenecid (10 mM), whereas the Vmax was not changed (125 +/- 19.2 pmol.s-1.mg-1 vs. 186 +/- 94 pmol.s-1.mg-1, P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				P. Arndt, C. Volk, V. Gorboulev, T. Budiman, C. Popp, I. Ulzheimer-Teuber, A. Akhoundova, S. Koppatz, E. Bamberg, G. Nagel, et al. Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1 Am J Physiol Renal Physiol, September 1, 2001; 281(3): F454 - F468. [Abstract] [Full Text] [PDF]

				C. E. Groves, M. Morales, and S. H. Wright Peritubular Transport of Ochratoxin A in Rabbit Renal Proximal Tubules J. Pharmacol. Exp. Ther., March 1, 1998; 284(3): 943 - 948. [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]

				Y. Deguchi, K. Nozawa, S. Yamada, Y. Yokoyama, and R. Kimura Quantitative Evaluation of Brain Distribution and Blood-Brain Barrier Efflux Transport of Probenecid in Rats by Microdialysis: Possible Involvement of the Monocarboxylic Acid Transport System J. Pharmacol. Exp. Ther., February 1, 1997; 280(2): 551 - 560. [Abstract] [Full Text]