Peritubular organic cation transport in isolated rabbit proximal tubules

C. E. Groves, K. K. Evans, W. H. Dantzler, S. H. Wright

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57 Scopus citations

Abstract

The physiological characteristics of peritubular organic cation transport were examined by measuring the transport of the organic cation tetraethylammonium (TEA) in rabbit renal proximal tubule suspensions and isolated nonperfused rabbit renal proximal tubules. Peritubular organic cation transport in both single S2 segments and suspensions of isolated renal proximal tubules was found to be a high-capacity, high-affinity, carrier- mediated process. For tubule suspensions, the maximal capacity of the carrier for TEA (J(max)) and the concentration of TEA at 1/2 J(max) (K(t)) (1.49 = 0.21 nmol · min-1 · mg dry wt-1 and 131 ± 16 μM, respectively), did not differ significantly from those measured in single S2 segments (J(max), 1.16 ± 0.075 nmol · min-1 · mg dry wt-1; K(t), 108 ± 10 μM). In addition, the pattern of inhibition of peritubular TEA transport by long- chain n-tetraalkylammonium compounds (n = 1-5) was both qualitatively and quantitatively similar in single S2 segments and tubule suspensions, exhibiting an increase in inhibitory potency with increasing alkyl chain length. For example, in tubule suspensions, apparent Michael's constants for inhibition of TEA uptake ranged from 1.3 mM for tetramethylammonium (TMA) to 0.8 μM for tetrapentylammonium (TPeA). To determine whether these compounds were substrates for the peritubular organic cation transporter, their effect on the efflux of [14C]TEA from tubule suspensions was examined. A concentration of 0.5 mM of the short-chain tetraalkyls TMA or TEA increased the efflux of [14C]TEA (i.e., trans-stimulated) from tubules in suspension. The longer-chain tetraalkyls tetrapropylammonium, tetrabutylammonium, and TPeA all decreased the efflux of [14C]TEA from tubules in suspension; TPeA completely blocked efflux. Thus, in contrast to the inhibitory potency of these agents, the efficiency of their transport by the peritubular organic cation transporter appeared to decrease with increasing alkyl chain length.

Original languageEnglish (US)
Pages (from-to)F450-F458
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume266
Issue number3 35-3
DOIs
StatePublished - 1994

Keywords

  • kidney
  • tetraalkylammonium
  • tetraethylammonium

ASJC Scopus subject areas

  • Physiology

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