MODULATION OF ORGANIC CATION-TRANSPORT AND LIPID FLUIDITY BY BENZYL ALCOHOL IN RAT RENAL BRUSH-BORDER MEMBRANES

Purpose. Organic cations are actively transported in renal brush-borde r membranes (BBM) by the H+/organic cation antiport system. In the pre sent study, we investigated the relationship between membrane fluidity and organic cation transport in the BBM. Methods. The effects of benz yl alcohol, a membrane fluidizing agent, on the organic cation tetraet hylammonium (TEA) uptake were studied using renal BBM vesicles isolate d from rat kidney. BBM fluidity was assessed by fluorescence polarizat ion technique. Results. H+ gradient-dependent uptake of TEA in BBM ves icles was inhibited by benzyl alcohol in a dose-dependent manner, with an apparent half inhibitory concentration of 18mM. The decrease in fl uorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene in BBM, which r epresents the increase in membrane fluidity, was correlated with the d ecrease in TEA transport activity. The dissipation rate of H+ gradient , a driving force for organic cation transport in BBM, was increased b y benzyl alcohol. In addition, H+ gradient-independent TEA-TEA exchang e was also inhibited by benzyl alcohol. These findings indicate that b enzyl alcohol inhibits the uptake of TEA by affecting the intrinsic ac tivity of the organic cation transporter and the H+ gradient dissipati on rate. Conclusions. The membrane fluidity should be an important det erminant for organic cation transport in renal BBM.