Transport of the organic cation N1-methylnicotinamide by the rabbit proximal tubule. I. Accumulation in the isolated nonperfused tubule.
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.
Besseghir
K
K
Institut de Pharmacologie de l'Université de Lausanne, Switzerland.
Mosig
D
D
Roch-Ramel
F
F
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
D009536:Niacinamide; D011190:Potassium Cyanide; C024058:N(1)-methylnicotinamide; D010130:p-Aminohippuric Acid