Liver ganglioside storage after perhexiline maleate.
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Biomedical subjects
Publications and source records attributed to R Poupon.
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The purpose of this work was to validate for taurocholate and taurochenodeoxycholate the multiple infusion method of Wheeler et al. previously used for the study of hepatic sulphobromophthalein transport and to obtain numerical estimates of the relative storage capacity and secretory transport maximum of both bile acids. Experiments were performed in anaesthetized dogs after depletion of the endogenous bile acid pool. Bile was collected continuously to prevent recirculation of bile acids and to measure their secretion rates. Taurocholate or taurochenodeoxycholate were infused intravenously at 3 different rates and blood samples were collected every ten min to measure serum bile acid concentrations. Extrahepatic distribution spaces of taurocholate and taurochenodeoxycholate were measured by an isotope dilution method. Serum bile acid concentrations varied linearly with time during the last 30 min of each infusion period. A linear relationship was found between the calculated hepatic removal rate and the rate of change of serum bile acid concentration. The mean values of relative storage capacity were (in mumol.mumol-1.l-1.kg body weight-1) 0.16 +/- SD 0.07 for taurocholate and 0.08 +/- SD 0.03 for taurochenodeoxycholate. The mean values for secretory transport maximum were (in mumol.min-1.kg body weight-1) 4.81 +/- SD 1.24 for taurocholate and 3.56 +/- SD 0.60 for taurochenodeoxycholate. The values of secretory transport maximum with the multiple infusion method were only slightly higher than those obtained by direct measurement of biliary secretion. The values of relative storage capacity obtained during infusions resulting in decreasing plasma concentrations were usually lower than those obtained when the plasma concentration increased. This suggests that the limitations of the method previously noted for sulphobromophthalein may apply to bile acids.
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The relationship between taurocholate or taurochenodeoxycholate secretion and cholesterol and phospholipid secretion in bile was studied in anaesthetized dogs infused with graded doses of these bile acids. Cholesterol output was linearly related to bile acid output during both taurocholate and taurochenodeoxycholate infusions. On the average 1.45 nmol and 4.70 nmol of cholesterol were secreted per mumol of taurocholate or taurochenodeoxycholate respectively (P less than 0.001). A linear relationship was also observed between phospholipid secretion rate and taurocholate or taurochenodeoxycholate secretion rates. However, the amounts of phospholipid secreted per mumol of taurocholate or taurochenodeoxycholate (respectively 0.10 and 0.15 mumol) were not significantly different. Thus, bile was less saturated with cholesterol during taurocholate infusions than during taurochenodeoxycholate infusions. These results are consistent with the hypothesis that micelle formation by bile acids is a major determinant of cholesterol and phospholipid secretion in the dog.
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Purified adipocytes plasma membranes have been prepared from human adipose tissue. The presence of an adenylate cyclase sensitive to epinephrine and fluoride has been demonstrated. Activation of the adenylate cyclase was usually 2 to 4 fold in the presence of epinephrine 5.10-5M and 8 to 10 fold in the presence of fluoride 10 mM. The adenylate cyclase from human adipose tissue was insensitive to glucagon and ACTH; these results are in support of previous studies of lipolysis in isolated fact cells or tissue fragments from human adipose tissue.
1. The influence of lysine acetylsalicylate on bile flow, erythritol clearance and bile salt, phospholipid and cholesterol secretion in bile was studied in unanaesthetized dogs fitted with a Thomas duodenal cannula. 2. Lysine acetylsalicylate induced a marked increase in bile flow and a parallel increase in erythritol clearance although the bile salt secretion remained unchanged; this suggests that the compound stimulated the formation of the canalicular (hepatocytic) bile salt-independent fraction of bile flow. 3. Lysine acetylsalicylate induced a significant decrease in biliary phospholipid and cholesterol secretion and the cholesterol saturation of bile was significantly reduced. 4. It is postulated that the decrease in phospholipid and cholesterol secretion resulted from the dilution of intracanalicular bile salts. This effect of lysine acetylsalicylate, and possibly of other bile salt-independent choleretics, may be of value in the treatment of cholesterol gallstones in man.
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