Substrate structure exerts little effect on binding to the organic cation/H+ exchanger of rabbit renal luminal membranes

Stephen Wright, T. M. Wunz

Research output: Contribution to journalArticle

Abstract

The kidney secretes organic cations (OCs) and the active step involves OC/H+ exchange in the luminal membrane of proximal cells. Although lipophilicity is an important criterion for binding of substrates to this transporter (Pflügers Arch, 429:313, 1995), the steric influence of substrate structure is unclear. We examined this issue by measuring the inhibition of OC/H+ exchange produced by structurally-related OCs. OC/H+ exchange was determined by measuring transport of [14C]tetraethylammonium (TEA) in brush-border membranes from renal cortex. Transport was measured in the presence of a pH gradient (pHin 6.0; pHout 7.5) to maximize TEA/H+ exchange. We tested the hypothesis that a systematic shift of molecular mass, from a longitudinal to latitudinal axis (relative to a fixed cationic 'nucleus'), systematically influences the inhibitory effectiveness of our test agents: a series of 4-phenyl and 3-phenyl pyridinium and quinolinium compounds. The 'R' groups on the quaternary nitrogen ranged from a phenyl moiety (most lipophilic) to a -CH2-CH2OH moiety (least lipophilic). Inhibitory constants (apparent Kis) for these compounds ranged from ∼1 μM to ∼50 μM. There was a strong correlation between lipophilicity of each compound and its inhibitory effectiveness. There was, however, no clear correlation between longitudinal vs. latitudinal distribution of steric mass and the inhibitory effectiveness of the test substrates. We conclude that steric factors have comparatively little effect on binding of substrates to the renal OC/H+ exchanger.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

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Cations
cations
rabbits
kidneys
Rabbits
Membranes
Kidney
Substrates
Tetraethylammonium
hydrophobicity
Quinolinium Compounds
Pyridinium Compounds
Proton-Motive Force
Molecular mass
Arches
Brushes
Microvilli
microvilli
transporters
cortex

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Substrate structure exerts little effect on binding to the organic cation/H+ exchanger of rabbit renal luminal membranes. / Wright, Stephen; Wunz, T. M.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

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