A target for cholesterol absorption inhibitors in the enterocyte brush border membrane

Biochim Biophys Acta. 2000 Jul 19;1486(2-3):243-52. doi: 10.1016/s1388-1981(00)00068-8.


Uptake of cholesterol by the intestinal absorptive epithelium can be selectively blocked by specific small molecules, like the sterol glycoside, L-166,143. Furthermore, (3)H-labeled L-166,143 administered orally to hamsters binds specifically to the intestinal mucosa, suggesting the existence of a cholesterol transporter. Using autoradiography, the binding site of (3)H-L-166,143 in the hamster small intestine was localized to the very apical aspect of the absorptive epithelial cells. Label was competed by non-radioactive L-166,143 and two structurally distinct cholesterol absorption inhibitors, suggesting a common site of action for these compounds. L-166,143 blocked uptake of (3)H-cholesterol into enterocytes in vivo, as demonstrated by autoradiography, suggesting that it inhibits a very early step of cholesterol absorption, incorporation into the brush border membrane. This conclusion was confirmed by studies in which intestinal brush borders were isolated from hamsters dosed with (3)H-cholesterol in the presence or absence of L-166,143. Uptake of (3)H-cholesterol into the membranes was substantially inhibited by the compound. In contrast, an inhibitor of acyl CoA:cholesterol acyltransferase, did not affect uptake of (3)H-cholesterol into the brush border membranes. These results strongly support the existence of a specific transporter that facilitates the movement of cholesterol from bile acid micelles into the brush border membranes of enterocytes.

MeSH terms

  • Animals
  • Anticholesteremic Agents / pharmacology*
  • Autoradiography
  • Bile Acids and Salts / metabolism
  • Binding Sites
  • Biological Transport / drug effects
  • Cholesterol, Dietary / metabolism*
  • Cricetinae
  • Down-Regulation
  • Duodenum / drug effects
  • Duodenum / metabolism
  • Ileum / drug effects
  • Ileum / metabolism
  • Intestinal Absorption / drug effects*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / ultrastructure
  • Jejunum / drug effects
  • Jejunum / metabolism
  • Male
  • Mesocricetus
  • Microvilli / drug effects
  • Microvilli / metabolism
  • Saponins / metabolism
  • Saponins / pharmacology*
  • Spirostans*
  • Tritium


  • Anticholesteremic Agents
  • Bile Acids and Salts
  • Cholesterol, Dietary
  • L 165313
  • L 166143
  • Saponins
  • Spirostans
  • Tritium