Effects of Bay o 2752, a hypocholesterolemic agent, on intestinal taurocholate absorption and cholesterol esterification.

摘要: Bay o 2752 [N,N'-(1, 11-undecandiyl)bis(2,3-dihydro-2-methyl-1H-indole-1-carboxamide)] has been demonstrated in rats to inhibit intestinal cholesterol absorption. Studies were carried out male Wistar determine if the mechanism is inhibition of bile acid absorption or esterification. did not alter as measured by vitro uptake [14C]taurocholic into ileal everted sacs (0.01 and 1.0 mg/ml 2752) biliary excretion radioactivity after vivo perfusion drug (1.0 at ml/min for 1 hr). Cholesterol esterification was determined measurement activity acyl coenzyme A:cholesterol acyltransferase from hepatic microsomes ester hydrolase pancreatic supernatant, lymphatic output cholesteryl intraduodenal infusion. Addition (0.01-10 micrograms/ml) produced a concentration-dependent decrease with an IC50 0.95 micrograms/ml. unaffected (1.0-100 micrograms/ml). Intraduodenal infusion (10 0.9 ml/hr 8 hr) reduced markedly flux lumen mesenteric lymph, especially esterified form both radioisotopically labeled total cholesterol. These data suggest that 2752-induced reduction results its potent inhibitory effect on activity.