A choline transporter in renal brush-border membrane vesicles: Energetics and structural specificity

Stephen Wright, Theresa M. Wunz, Timothy P. Wunz

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Abstract

Choline is a quaternary ammonium compound that is normally reabsorbed by the renal proximal tubule, despite its acknowledged role as a substrate for the renal organic cation (OC) secretory pathway. The basis for choline reabsorption was examined in studies of transport in rabbit renal brush-border membrane vesicles (BBMV). Although an outwardly directed H+ gradient (pH 6.0in : 7.5out) stimulated uptake of tetraethylammonium (TEA), a model substrate of the OC/H+ exchanger in renal BBMV, it had no effect on uptake of 1 μm choline. A 5 m mtrans concentration gradient of choline did, however, drive countertransport of both TEA and choline, although trans TEA had no effect on choline accumulation in BBMV. A 20 m m concentration of unlabeled choline blocked uptake of both choline and TEA by >85%, whereas 20 m m TEA blocked only TEA uptake. The kinetics of choline uptake into vesicles preloaded with 1 m m unlabeled choline appeared to involve two, saturable transport processes, one of high affinity for choline (Kt of 97 μm) and a second of low affinity (Ktof ∼10 m m), the latter presumably reflecting a weak interaction of choline with the OC/H+ exchanger. An inside-negative electrical PD stimulated the rate of uptake and supported the transient concentrative accumulation of choline in BBMV. The high affinity transporter showed a marked specificity for choline and closely related analogues. A model of the molecular determinants of substrate-transporter interaction is described. We conclude that the electrogenic high affinity pathway plays a central role in renal reabsorption of choline.

Original languageEnglish (US)
Pages (from-to)51-65
Number of pages15
JournalThe Journal of Membrane Biology
Volume126
Issue number1
DOIs
Publication statusPublished - Feb 1992

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Keywords

  • choline
  • kidney
  • molecular modeling
  • organic cation
  • proximal tubule
  • reabsorption
  • secretion
  • TEA
  • transport

ASJC Scopus subject areas

  • Physiology
  • Cell Biology
  • Biophysics

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