Influence of bile acid structure on bile flow and biliary lipid secretion in the hamster

Abstract

A comprehensive study of the influence of bile acid structure on bile flow and biliary lipid secretion was carried out by infusing pure bile acids at a physiological rate into the proximal small intestine of a bile fistula hamster. Twelve individual bile acids, cholate (C), ursocholate (UC), chenodeoxycholate (CDC), and ursodeoxycholate (UDC) as their glycine (G), taurine (T), or unconjugated form, were studied so that influence of the hydroxy substituents as well as side-chain structure could be defined. The pattern of bile acid output was dependent on bile acid structure and reflected the site and rate of intestinal absorption. Conjugated bile acid output was delayed because of late ileal absorption, and TUC was poorly absorbed. Unconjugated trihydroxy bile acids, C and UC, also exhibited a delay in absorption, while CDC and UDC were absorbed immediately and achieved the highest bile acid output. Unconjugated bile acids were conjugated initially mostly with taurine and then mostly with glycine. The effect of glycine conjugates of each bile acid on bile flow and biliary lipid secretion was similar to that of their corresponding taurine conjugates. All conjugated bile acids induced a similar rate of bile flow (9-15 microliter bile/mumol bile acid), but unconjugated bile acids other than C induced more flow (20-25 microliter bile/mumol bile acid) than their corresponding conjugates. Conjugates of the dihydroxy bile acids induced a greater secretion of phospholipid and cholesterol than cholyl conjugates, whereas conjugates of UC were unique in inducing extremely low phospholipid and cholesterol secretion. For an increase of 1 mumol X min-1 X kg-1 in bile acid output, the increase in phospholipid secretion was 0.072 mumol X min X kg for GCDC and TCDC; 0.051 mumol X min-1 X kg-1 for GUDC and TUDC; and 0.030 mumol X min-1 X kg-1 for GC and TC. Increase in cholesterol output per mumol X min-1 X kg-1 of bile acid output was 0.013 mumol X min-1 X kg-1 for GCDC and TCDC, 0.011 mumol X min-1 X kg-1 for GUDC and TUDC, and 0.005 mumol X min-1 X kg-1 for GC and TC. In general, unconjugated bile acids induced more phospholipid and cholesterol than their corresponding conjugates; however, the rank-order effect of the steroid nucleus substituents was similar to that observed for the respective conjugates. These results indicate that both nuclear and side-chain structure influence the enterohepatic circulation and biliary secretory properties of bile acids.(ABSTRACT TRUNCATED AT 400 WORDS)

Secretin activation of the apical Na+‐dependent bile acid transporter is associated with cholehepatic shunting in rats†

“…There is roughly a linear correlation between biliary bile acid and lipid secretion. 5 Thus, a doubling of TC flux through the canalicular membrane is consistent with the observed almost 2-fold increase in TC-dependent biliary secretion of cholesterol and phospholipid following secretin (Fig. 6).…”

“…4 Multiple passes of bile acids through the canalicular membrane leads to an increased bile acid biliary transit time, increased choleretic efficiency of bile acids (e.g., increased bile flow for each bile acid molecule secreted), and increased biliary lipid secretion. 5 We have characterized the transport activity of the apical Na ϩ -dependent bile acid transporter (ASBT) originally described in the ileum in isolated rat cholangio-cytes. 6 In addition, we have shown with immunofluorescence studies that ASBT is present in the apical membrane of large cholangiocytes and large (greater than 15 m in diameter) isolated intrahepatic bile duct units.…”

Bile salt–dependent efflux of cellular phospholipids mediated by ATP binding cassette protein B4

“…It has been reported that NaTC induces greater secretion of phospholipids and cholesterol than NaGC in hamsters. 26 The features of the PC and cholesterol secretion from HEK/ABCB4 cells were consistent with this observation.…”

Biliary secretion of anionic polypeptide fraction is not coupled to that of phospholipids and cholesterol in rats

“…A parameter that reflects the efficacy of bile acids to induce biliary lipid secretion is the (phospho-) bile flow and biliary phospholipid and cholesterol secretion rates decrease upon interruption of the enterohepatic circula-lipid-to-bile acid molar ratio. 28,37,38 Data presented in Fig. 3, however, indicate that a clear-cut relationship was not obtion by 54 { 14%, 74 { 13%, and 64 { 8%, respectively, parallel to the decrease in bile acid secretion rate (092 { served in any of the models between the phospholipid-to-bile acid molar ratio and the APF secretion rate.…”