REGULATION OF ABSORPTION OF CHOLESTEROL IN EPITHELIAL-CELLS OF HUMAN AND RAT SMALL-INTESTINE

Cholesterol absorption in human small intestine organ culture and rat small intestine epithelial cell culture IRD-98 was studied using [C-14 ]cholesterol, [H-3]cholesterol, and [C-14]sitosterol. Absorption of ch olesterol was shown to be a dose- and time-dependent specific process. Sitosterol absorption was concentration-independent, showed no time t rend, and accounted for approximately 25% of the total absorption of c holesterol. Monensin, an inhibitor of endocytosis, reduced the specifi c absorption of cholesterol by 37%. Absorption of cholesterol was stud ied under different conditions affecting its cellular metabolism. Load ing the IRD-98 cells with lipoprotein-free cholesterol resulted in a d ose-dependent decrease in cholesterol absorption. A similar effect was produced by administration of compound 58-035 (Sandoz), an inhibitor of acyl-CoA:cholesterol acyl transferase. Lovastatin, an inhibitor of 3-hydroxymethyl-3-glutaryl-CoA reductase, caused dose-dependent activa tion of cholesterol absorption. Loading the cells with cholesterol and administration of lovastatin or Sandoz 58-035 did not affect the abso rption of sitosterol. Human small intestine organ culture and the cult ure of rat small intestine IRD-98 cells proved useful as models to stu dy the absorption of cholesterol.