Effect of complete sulfation of bile acids on bile formation: role of conjugation and number of sulfate groups.
The effect of complete sulfation of conjugated cholic, chenodeoxycholic and deoxycholic acids on bile formation was investigated in rats. The sulfated bile acids were infused intravenously in stepwise increasing doses (1, 2, 3 and 4 mumol/min/100 gm body wt) in rats after 90 min of bile acid pool depletion. The effects of these bile acids on bile flow, bile salt, biliary phospholipid and cholesterol secretion rates were determined. In addition, their choleretic activity and their effect on biliary lipid secretion were calculated. Appropriate controls infused with nonsulfated bile were also performed. The sulfated bile acids increased bile flow with increasing the infusion doses, and the maximum bile flow was significantly higher than nonsulfated bile acids. Although cholestasis was developed during the infusion of nonsulfated bile acids, no cholestatic effect was observed for sulfated bile acids. With the exception of cholic acid, sulfation significantly increased the bile acid secretory rate maximum. The sulfates of chenodeoxycholic and deoxycholic acids were further hydroxylated. The choleretic activities for all the sulfated bile acids were significantly higher than the nonsulfated bile acids. All the sulfated bile acids significantly reduced the biliary lipid secretion, and a significant correlation was found between the choleretic activity and the phospholipid-dependent bile acid secretion. The data also showed that infusion of sulfated taurine-conjugated bile acids produced higher bile flow and bile acid secretion rate and was less effective when biliary lipid secretion rates were reduced compared with glycine conjugates. It is concluded that sulfated conjugated bile acids may have a role in protection during cholestasis either by stimulation of bile flow or by reduction of biliary lipid secretion, thus protecting cell membranes from the detergent properties of high concentrations of nonsulfated bile acids.
Yousef
I
I
Department of Pharmacology, University of Montreal, Sainte-Justine, Canada.
Mignault
D
D
Tuchweber
B
B
D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D001647:Bile Acids and Salts / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D002756:Cholagogues and Choleretics / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D019826:Cholic Acid; D002793:Cholic Acids / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000494:pharmacology; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013431:Sulfates / Q000378:metabolism*
D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D002793:Cholic Acids; D010743:Phospholipids; D013431:Sulfates; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D002784:Cholesterol; D019826:Cholic Acid