Differing effects of norcholate and cholate on bile flow and biliary lipid secretion in the rat

1984 ◽  
Vol 246 (1) ◽  
pp. G67-G71
Author(s):  
E. R. O'Maille ◽  
S. V. Kozmary ◽  
A. F. Hofmann ◽  
D. Gurantz
Keyword(s):  
Bile Acid ◽  
Acid Secretion ◽  
Bile Acids ◽  
Bile Flow ◽  
Critical Micellar Concentration ◽  
Biliary Lipid ◽  
Lipid Secretion ◽  
Unit Increase ◽  
Cholesterol Secretion ◽  
Bile Acid Secretion

The effects of norcholate (a C23 bile acid that differs from cholate in having a side chain containing four rather than five carbon atoms) on bile flow and biliary lipid secretion were compared with those of cholate, using the anesthetized rat with a bile fistula. Norcholate and cholate were infused intravenously over the range of 0.6-6.0 mumol X min-1 X kg-1. Both bile acids were quantitatively secreted into bile; norcholate was secreted predominantly in unconjugated form in contrast to cholate, which was secreted predominantly as its taurine or glycine conjugates. The increase in bile flow per unit increase in bile acid secretion induced by norcholate infusion [17 +/- 3.2 (SD) microliters/mumol, n = 8] was much greater than that induced by cholate infusion (8.6 +/- 0.9 microliters/mumol, n = 9) (P less than 0.001). Both bile acids induced phospholipid and cholesterol secretion. For an increase in bile acid secretion (above control values) of 1 mumol X min-1 X kg-1, the increases in phospholipid secretion [0.052 +/- 0.024 (SD) mumol X min-1 X kg-1, n = 9] and cholesterol secretion (0.0071 +/- 0.0033 mumol X min-1 X kg-1, n = 9) induced by norcholate infusion were much less than those induced by cholate infusion (0.197 +/- 0.05 mumol X min-1 X kg-1, n = 9, and 0.024 +/- 0.011 mumol X min-1 X kg-1, n = 9, respectively; P less than 0.001 for both phospholipid and cholesterol). The strikingly different effects of norcholate on bile flow and biliary lipid secretion were attributed mainly to its possessing a considerably higher critical micellar concentration than cholate.

Effect of primary bile acids on bile lipid secretion from perfused dog liver

1975 ◽  
Vol 229 (3) ◽  
pp. 714-720 ◽  
Author(s):  
NE Hoffman ◽  
DE Donald ◽  
AF Hosmann
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Liver Perfusion ◽  
Biliary Lipid ◽  
Hepatic Extraction ◽  
Perfusion Technique ◽  
Lipid Secretion ◽  
Cholesterol Secretion ◽  
Dog Liver ◽  
Bile Acid Secretion

An isolated canine liver perfusion technique featuring a second dog as the pump oxygenator was used to compare biliary lipid secretion during randomized, steady-state perfusions at two different rates of cholyl taurine or chenodeoxycholyl taurine infusions. The hepatic extraction of the trihydroxy-conjugated bile acid was considerably greater than that of the dihydroxy conjugate, possibly explained by ultrafiltration experiments which indicated that cholyl taurine was less protein bound than chenodeoxycholyl taurine. Both bile acids induced phospholipid and cholesterol secretion that was linearly proportional to bile acid secretion. However, each mole of secreted chenodeoxycholyl taurine induced a greater relative secretion of phospholipid and cholesterol than did that of cholyl taurine. Thus in the canine liver, the two primary bile acids are extracted at different rates and induce biliary secretion of different relative lipid composition.

Differing effects of hydroxy-7-oxotaurine-conjugated bile acids on bile flow and biliary lipid secretion in dogs

1984 ◽  
Vol 246 (2) ◽  
pp. G166-G172
Author(s):  
R. G. Danzinger ◽  
M. Nakagaki ◽  
A. F. Hofmann ◽  
E. B. Ljungwe
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Bile Flow ◽  
Critical Micellar Concentration ◽  
Independent Effect ◽  
Biliary Lipid ◽  
Compound I ◽  
Lipid Secretion ◽  
The Individual

The effects on bile flow and biliary lipid secretion of two taurine-conjugated 7-oxo bile acids, 3 alpha-hydroxy-7-oxocholanoyltaurine (I) and 3 alpha,12 alpha-dihydroxy-7-oxocholanoyltaurine (II), were measured in the unanesthetized, chronic bile fistula dog. Each synthetically prepared compound, or cholyltaurine as control, was infused intravenously at a physiological rate of 1 mumol X kg-1 X min-1 for randomized 90-min periods. Bile samples were collected and analyzed for biliary lipids (bile acids, phospholipid, and cholesterol) and bile acid composition. Both compounds were secreted efficiently in bile, recovery averaging 90%. The trisubstituted compound (II) induced a greater choleresis and less phospholipid and cholesterol secretion than the disubstituted compound (I) or cholyltaurine. Each oxo compound was partially reduced during hepatic passage: about 47% of I (to mostly chenodeoxycholyltaurine) and about 30% of II (to mostly cholyltaurine). The effect of the individual bile acids on biliary lipid secretion was then calculated by assuming that a) the infused bile acid induced biliary lipid secretion after its hepatic biotransformation and b) each bile acid or its biotransformation product exerted an independent effect on biliary lipid secretion (expressed as a linkage coefficient, e.g., phospholipid secretion/bile acid secretion). For phospholipid, the calculated linkage coefficient for I was 0.31; for II, 0.07. For cholesterol, the calculated linkage coefficient for I was 0.014; for II, 0.003. In vitro studies indicated that the critical micellar concentration (CMC) in 0.15 M Na+ was 22 mM for I and 40 mM for II (compared with 6 mM for cholyltaurine.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Lipid Secretion in Obese and Non-Obese Individuals with and without Gallstones

1985 ◽  
Vol 69 (1) ◽  
pp. 71-79 ◽  
Author(s):  
A. Reuben ◽  
P. N. Maton ◽  
G. M. Murphy ◽  
R. H. Dowling
Keyword(s):  
Bile Acid ◽  
Acid Secretion ◽  
Biliary Lipid ◽  
Biliary Cholesterol ◽  
Cholesterol Gallstones ◽  
Lipid Secretion ◽  
Biliary Cholesterol Secretion ◽  
Cholesterol Secretion ◽  
Bile Acid Secretion ◽  
Secretion Rates

1. Biliary lipid secretion rates were measured in non-obese and obese individuals with and without cholesterol gallstones, using a steady-state, amino acid duodenal perfusion method. In addition, biliary lipid secretion rates were measured in five obese gallstone patients receiving high-dose chenodeoxycholic acid therapy (16-22 mg day−1 kg−1). 2. Bile acid secretion rates in the non-obese patients with cholesterol gallstones (563+sem 70 μmol/h, n = 6) were significantly lower than in the non-obese controls (1078 + 210 μmol/h, n = 10, P < 0.05), whereas cholesterol secretion rates were similar in the non-obese individuals with and without gallstones (51+7 and 42+4 μmol/h respectively). 3. In the obese, both with and without gallstones, the major abnormality was hypersecretion of cholesterol (107+7 μmol/h, n = 7, and 81 + 15 μmol/h, n = 7, respectively). Both these values were significantly greater than those in the non-obese controls (P < 0.01-0.02). 4. Biliary cholesterol secretion rates correlated significantly with bile acid secretion rates but, for every mole of bile acid secreted, the obese secreted more cholesterol than the non-obese. 5. Chenodeoxycholic acid treatment lowered biliary cholesterol saturation in obese gallstone patients by reducing biliary cholesterol secretion. 6. These results suggest that there are two major types of defect in biliary lipid secretion in gallstone patients: reduced biliary bile acid secretion in non-obese gallstone patients and excessive biliary cholesterol secretion in the obese.

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

1984 ◽  
Vol 247 (6) ◽  
pp. G736-G748 ◽  
Author(s):  
D. Gurantz ◽  
A. F. Hofmann
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Bile Flow ◽  
Enterohepatic Circulation ◽  
Acid Output ◽  
Chain Structure ◽  
Side Chain ◽  
Biliary Lipid ◽  
Lipid Secretion ◽  
Acid Structure

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)

Effects of individual taurine-conjugated bile acids on biliary lipid secretion and sucrose clearance in the unanesthetized dog

1982 ◽  
Vol 242 (1) ◽  
pp. G40-G46 ◽  
Author(s):  
I. T. Gilmore ◽  
J. L. Barnhart ◽  
A. F. Hofmann ◽  
S. Erlinger
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Bile Flow ◽  
Hydroxyl Group ◽  
Biliary Lipid ◽  
Apparent Permeability ◽  
Steroid Nucleus ◽  
Bile Fistula ◽  
Cholesterol Secretion ◽  
Conjugated Bile Acids

The effect of three taurine-conjugated bile acids on bile flow, induced biliary secretion of phospholipids and cholesterol, and the hepatobiliary clearance from plasma of sucrose and erythritol (two uncharged, nonmetabolizable permeability probe molecules) was assessed in the unanesthetized bile fistula dog under steady-state conditions. Synthetically prepared chenodeoxycholyltaurine, cholytaurine, or urological rate for randomized 90-min periods, and four 10-min samples of bile were taken at the end of each period. Induced bile flow (per mumoles of bile acid) was calculated to be about one-third higher with ursodeoxycholyltaurine than with the other bile acids. Induced phospholipid secretion was identical for all bile acids, but cholesterol secretion differed: the two dihydroxy taurine conjugates induced considerably more cholesterol per molecule bile acid or phospholipid than colyltaurine. Further, ursodeoxycholyltaurine induced significantly more cholesterol secretion than chenodeoxycholyltaurine. Erythritol clearances were identical for all bile acids, and sucrose clearance, although slightly higher for chenodeoxycholyltaurine than ursodeoxycholyltaurine, was similar for all three conjugated bile acids. The results indicate that, for these two 3,7-dihydroxy bile acids, the orientation of the 7-hydroxyl group on the steroid nucleus has a marked influence on cholesterol secretion into bile and bile flow but not on the apparent permeability of the hepatobiliary tree.

Mechanism of bile acid-induced biliary lipid secretion in the rat: effect of conjugated bilirubin

1993 ◽  
Vol 264 (3) ◽  
pp. G462-G469 ◽  
Author(s):  
H. J. Verkade ◽  
R. Havinga ◽  
A. Gerding ◽  
R. J. Vonk ◽  
F. Kuipers
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Genetic Defect ◽  
Specific Interaction ◽  
Biliary Secretion ◽  
Biliary Lipid ◽  
Bile Acid Concentration ◽  
Lipid Secretion ◽  
Cholesterol Secretion ◽  
Conjugated Bilirubin

We have compared the effects of bilirubin and bilirubin ditaurate (BDT) on biliary phospholipid and cholesterol secretion in unanesthetized normal Wistar (NW) and Groningen Yellow (GY) Wistar rats under various experimental conditions. GY rats express a genetic defect in biliary secretion, but not in hepatic uptake, of various organic anions. Under physiological conditions, NW and GY rats showed similar biliary secretion rates of bile acids and of bilirubin, despite the fact that bilirubin concentrations in GY plasma were 25 times as high and in GY livers three times as high as in NW plasma and livers, respectively. Secretion of cholesterol and phospholipids was not impaired in GY rats under these conditions. Biliary secretion of intravenously injected BDT (3 mumol/100 g body wt) was delayed in eight-day bile-diverted GY rats and showed lower peak values when compared with NW rats. The inhibitory effects of BDT on phospholipid and cholesterol secretion paralleled these differences, being delayed and much less pronounced in GY rats. No overshoot in phospholipid or cholesterol secretion was observed when bilirubin output returned to preinjection values. Stimulation of [14C]choline-labeled phospholipid secretion after a bolus injection of taurochenodeoxycholic acid (1 mumol/100 g body wt) closely followed biliary bile acid concentration. Similarly, inhibition of labeled phospholipid secretion by BDT closely paralleled the biliary bilirubin concentration. Gel filtration studies (Sepharose 4B-CL) under micelle-preserving conditions demonstrated a specific interaction of BDT with biliary bile acids. The presented data indicate that conjugated bilirubin does not inhibit biliary lipid secretion via interaction with bile acids inside the hepatocyte.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals UNCOUPLING OF BILIARY LIP ID SECRETION FROM BILE ACID SECRETION BY ORGANIC ANIONS, DUE TO INTRACANALICULAR INTERACTION WITH BILE ACIDS

1989 ◽  
Vol 26 (3) ◽  
pp. 282-282
Author(s):  
H J Verkade ◽  
M J Wolbers ◽  
R Havinga ◽  
R J Vonk ◽  
F Kuipers
Keyword(s):  
Bile Acid ◽  
Acid Secretion ◽  
Bile Acids ◽  
Organic Anions ◽  
Bile Acid Secretion
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