Bile acid sulfonate and 7-alkylated bile acid analogs: effect on intestinal absorption of taurocholate and cholesterol 7alpha-hydroxylase activity in cultured rat hepatocytes.
The effects of sulfonate analogs of cholic (C), chenodeoxycholic (CDC), and ursodeoxycholic acid (UDC) and three 7-alkylated CDCs--7-methyl-, 7-ethyl-, and 7-propyl-CDCs--on taurocholate absorption from rat terminal ileum in situ and on cholesterol 7alpha-hydroxylase activity in primary culture of the rat liver were investigated. The sulfonate analogs of two dihydroxy bile acids CDC and UDC, but not C, significantly decreased the absorption of taurocholate. Taurine conjugates of 7-alkylated CDC slightly decreased the taurocholate absorption, and tauro-7-propyl-CDC significantly suppressed the absorption. Although the sulfonate analogs of C and CDC reduced cholesterol 7alpha-hydroxylase activity by 40% and 60% compared to control, UDC-sulfonate analog did not affect enzymatic activity. These results were consistent with those of the lead compounds, C, CDC, and UDC. The introduction of methyl group at C-7 position of CDC attenuated the reduction in cholesterol 7alpha-hydroxylase activity by CDC. However, elongation of the alkyl group resulted in an inhibitory effect. The present study revealed the following: 1) bile acid sulfonates act on cholesterol and bile acid metabolism in a similar manner as taurine conjugated bile acids; and 2) the biologic properties of CDC could be altered by the introduction of alkyl group at C-7 position.
Kim
H G
HG
Institute of Pharmaceutical Science, Hiroshima University School of Medicine, Japan.
Une
M
M
Hino
A
A
Wada
H
H
Yoshii
M
M
Kuramoto
T
T
Fujimura
K
K
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism*; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D013451:Sulfonic Acids / Q000378:metabolism; D013656:Taurocholic Acid / Q000378:metabolism*
D001647:Bile Acids and Salts; D013451:Sulfonic Acids; D013656:Taurocholic Acid; D007770:L-Lactate Dehydrogenase; D002790:Cholesterol 7-alpha-Hydroxylase