Mechanistic Studies on Effect of Cholate Concentration on Cholesterol Uptake by Isolated Rabbit Intestine

Abstract

A novel apparatus was designed to measure the uptake of cholesterol by mounted and isolated segments of rabbit intestine. The system maintained constant hydrodynamic conditions at the exposed mucosal surfaces. Cholesterol uptake was studied in a series of Ringer's solutions containing different cholate concentrations. The data indicated a substantial effect of cholate on cholesterol transport. A simple semi-infinite sink model in conjunction with theoretical equations on a first-order transport process was proposed. First-order uptake rate constants for the early experimental data points were calculated for the various cholesterol-cholate systems. At 4.64 mM cholate, there was approximately a 190 times increase in the relative initial uptake rate compared to the 0 mM cholate level. Above the CMC of cholate, there was a decrease in the cholesterol uptake. The diffusion coefficients of cholesterol in the various cholate media varied between 3.6 and 13.0 X 10−6 cm2/sec, which were in the range of 4.0 X 10−6 cm2/sec calculated by the Stokes-Einstein approximation. The calculated permeability coefficients of cholesterol, below and above the CMC of cholate, were on the order of 0.8-9.0 X 10−2 cm/sec.