Abstract
Organic cations are actively transported in renal brush-border membranes (BBM) by the H+/organic cation antiport system. In the present study, we investigated the relationship between membrane fluidity and organic cation transport in the BBM. The effects of benzyl alcohol, a membrane fluidizing agent, on the organic cation tetraethylammonium (TEA) uptake were studied using renal BBM vesicles isolated from rat kidney. BBM fluidity was assessed by fluorescence polarization technique. H+ gradient-dependent uptake of TEA in BBM vesicles was inhibited by benzyl alcohol in a dose-dependent manner, with an apparent half inhibitory concentration of 18mM. The decrease in fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene in BBM, which represents the increase in membrane fluidity, was correlated with the decrease in TEA transport activity. The dissipation rate of H+ gradient, a driving force for organic cation transport in BBM, was increased by benzyl alcohol. In addition, H+ gradient-independent TEA-TEA exchange was also inhibited by benzyl alcohol. These findings indicate that benzyl alcohol inhibits the uptake of TEA by affecting the intrinsic activity of the organic cation transporter and the H+ gradient dissipation rate. The membrane fluidity should be an important determinant for organic cation transport in renal BBM.
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