title: Transport of the organic cation N1-methylnicotinamide by the rabbit proximal tubule. I. Accumulation in the isolated nonperfused tubule.
abstract: 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.
authors: Institut de Pharmacologie de l'Université de Lausanne, Switzerland.
authors: K
authors: K
authors: Besseghir
authors: D
authors: D
authors: Mosig
authors: F
authors: F
authors: Roch-Ramel
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D005260:Female; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D011190:Potassium Cyanide / Q000494:pharmacology; D011817:Rabbits; D010130:p-Aminohippuric Acid / Q000032:analysis / Q000493:pharmacokinetics
chemical_list: D009536:Niacinamide; D011190:Potassium Cyanide; C024058:N(1)-methylnicotinamide; D010130:p-Aminohippuric Acid