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Transport of the organic cation N1-methylnicotinamide by the rabbit proximal tubule. I. Accumulation in the isolated nonperfused tubule

K Besseghir, D Mosig and F Roch-Ramel

Institut de Pharmacologie de l'Universite de Lausanne, Switzerland.

Isolated nonperfused rabbit renal proximal tubules were used to investigate the basolateral step of transport of the organic cation N1- methylnicotinamide (NMN). NMN accumulation was highest and saturable in S2 and S3 segments, but lowest and nonsaturable in S1 segments. In S1 segments, accumulation of [3H]-NMN (0.5-8 microM in the bath) resulted in an average tubular water/medium concentration ratio (T/M) of 8.2, whereas in S2 and S3 segments T/M averaged 19.5 and 18.6, respectively. At these concentrations, about 30% of the label was attached in all segments to a metabolite comigrating with nicotinamide. KCN (10(-2) M) or ouabain (10(-4) M) reduced T/M to about 8 for all segments. NMN accumulation was inhibited (to a T/M of about 3 with mepiperphenidol) by other organic cations (10(-5)-10(-3) M) with the potency sequence mepiperphenidol greater than tetraethylammonium = quinine greater than morphine, these organic cations having no effect on p-aminohippurate accumulation, except for the highest concentration of quinine (10(-3) M). After correction for metabolism, NMN accumulation could be accounted for by simple electrochemical equilibrium across the basolateral membrane. The basolateral step of NMN transport appears therefore to be a carrier-mediated diffusion, in opposition to the active basolateral accumulation described for tetraethylammonium.

Volume 253, Issue 2, pp. 444-451, 05/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


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 Drug Metab. Dispos.Home page
F. Pietruck, M. Horbelt, T. Feldkamp, K. Engeln, S. Herget-Rosenthal, T. Philipp, and A. Kribben
DIGITAL FLUORESCENCE IMAGING OF ORGANIC CATION TRANSPORT IN FRESHLY ISOLATED RAT PROXIMAL TUBULES
Drug Metab. Dispos., March 1, 2006; 34(3): 339 - 342.
[Abstract] [Full Text] [PDF]


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Copyright © 1990 by the American Society for Pharmacology and Experimental Therapeutics.