Bile salt-induced increases in duodenal brush-border membrane proton permeability, fluidity, and fragility

Abstract

Rabbit duodenal brush-border membrane vesicles were treatedin vitro with deoxycholate, glycodeoxycholate, or taurodeoxycholate. Intravesicular [¹⁴C]glucose space at equilibrium, 0.54 μl/mg protein, was reduced by exposure to the three bile salts in a concentration (0.1–5.0 mM) -dependent manner, equatable with increased membrane fragility. Net proton permeability (P_net), determined by acridine orange fluorescence quenching, was increased from 6.3 × 10⁻⁴ cm/sec in untreated vesicles, by approximately 120, 150, and 170%, by treatment with bile salts at 0.1, 0.5 and 1.0 mM, respectively. The three bile salts were equipotent. The increases in membrane fragility andP _{net were not accompanied by significant increases in membrane fluidity, as assessed from steady-state and time-resolved diphenylhexatriene fluorescence anisotropy. The data demonstrate direct effects of bile salts on duodenal apical membrane fragility and proton permeability that are likely to be early events in bile salt-induced mucosal damage}.