Mucosal uptake in vitro of cholesterol from bile salt and surfactant solutions

Abstract

That bile salts are required for intestinal absorption of cholesterol is well known, but the mechanism of action is elusive. Substitution of other surfactant micelles and inclusion of fatty acid or monoglyceride variably influenced sterol transport. In this study, rat jejunal mucosal sheets were exposed for 1-2 min to 10 mM micellar solutions of taurodeoxycholate, dodecylsulfate, Tween 80 or cetyltrimethylammonium bromide containing cholesterol, 0.25 mM. Monoolein and/or oleic acid were variably added. Cholesterol influx was insignificant in all solubilizers without additives. With taurodeoxycholate, addition of monoolein progressively enhanced influx from 13 nmoles/cm-2 per hour to 29 nmoles/cm-2 per hour (0.67-5.4 mM monoglyceride). Oleic acid, 3 mM, was as effective as 5.4 mM monoolein. Oleic acid, 3 mM, added to monoolein 3 mM maximized influx (42 nmoles/cm-2 per hour). With cetyltrimethylammonium bromide, monoolein 0.67 mM enhanced influx to 13 nmoles/cm-2 per hour but further additions of monoolein with or without oleic acid had no added effect. Additives had no material effect on the insignificant influx from the other anionic or nonionic surfactants. These results are not explained by differences in cholesterol, monoolein or oleic acid partition or in micellar sizes. Specific interactions of bile salt and fatty acid or monoglyceride with the plasma membrane are postulated in cholesterol absorption.