The influence of conjugation of cholic acid on its uptake and secretion: hepatic extraction of taurocholate and cholate in the dog

O'Máille, E R; Richards, Toby; Short, A. H.

doi:10.1113/jphysiol.1967.sp008172

Cited by 89 publications

(34 citation statements)

References 14 publications

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“…2 Thus, the present results show that saturation of the hepatic bile acid uptake cannot be reached under physiologically occurring conditions in man. This concept is in agreement with data obtained from studies in the dog (24)(25)(26) and in the rat (21,27). The estimated fractional uptake of bile acids was reduced in one of our patients (No.…”

Section: Discussionsupporting

confidence: 82%

Hepatic Uptake of Bile Acids in Man

Angelin¹,

Björkhem²,

Einarsson³

et al. 1982

J. Clin. Invest.

200

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A B S T R A C T This investigation was undertaken inorder to (a) characterize the postprandial inflow of individual bile acids to the liver and (b) determine if peripheral venous bile acid levels always adequately reflect the portal venous concentration, or if saturation of hepatic bile acid uptake can occur under physiological conditions. In five patients with uncomplicated cholesterol gallstone disease, the umbilical cord was cannulated during cholecystectomy, and a catheter was left in the left portal branch for 5 to 7 d. The serum concentrations of cholic acid, chenodeoxycholic acid, and deoxycholic acid in portal venous and systemic circulation were then determined at intervals of 15 to 30 min before and after a standardized meal.A highly accurate and specific gas chromatographic/ mass spectrometric technique was used.The sum of the fasting concentrations of the three bile acids averaged 14.04±4.13 Amol/liter in portal venous serum, and 2.44±0.31 Amol/liter in peripheral venous serum. The estimated hepatic fractional uptake of cholic acid was -90%, and those of chenodeoxycholic acid and deoxycholic acid were 70-80%. This resulted in an enrichment of systemic bile acids in the dihydroxy bile acid species. In response to a standardized meal, portal venous bile acid concentrations increased two-to sixfold, with a peak seen 15-60 min after the meal. The maximum postprandial portal venous bile acid concentration averaged 43.04±6.12,umol/liter, and the corresponding concentration in peripheral serum was 5.22±0.74 A.mol/liter. The estimated fractional uptakes of the individual bile acids were not affected by the increased inflow to the liver. The peripheral venous concentrations of individual as

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Section: Discussionsupporting

confidence: 82%

Hepatic Uptake of Bile Acids in Man

Angelin¹,

Björkhem²,

Einarsson³

et al. 1982

J. Clin. Invest.

200

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“…A similar marked and rapid decrease in apo-B,E receptor binding was achieved by infusing bile acids into cholestyramine-treated dogs, as well as into immature dogs (Table IV). The infusion rate chosen was high enough to suppress bile acid biosynthesis almost totally, but still well below the maximum excretory capacity of the liver (32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

“…Suppression of bile acid formation would therefore considerably reduce the hepatic demand for cholesterol. Consequently, we investigated whether canine hepatic lipoprotein receptors were affected by the infusion of exogenous taurocholate, the major endogenous bile acid in the dog (32)(33)(34).…”

mentioning

confidence: 99%

Regulation of Hepatic Lipoprotein Receptors in the Dog. RAPID REGULATION OF APOLIPOPROTEIN B,E RECEPTORS, BUT NOT OF APOLIPOPROTEIN E RECEPTORS, BY INTESTINAL LIPOPROTEINS AND BILE ACIDS

Angelin¹,

Raviola²,

Innerarity³

et al. 1983

J. Clin. Invest.

112

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A B S T R A C T Two distinct lipoprotein receptors can be expressed in the dog liver. One is the apolipoprotein (apo-) B,E receptor. This receptor binds apo-B-containing low density lipoproteins (LDL), as well as apo-E-containing lipoproteins, such as the cholesterol-induced high density lipoproteins (HDL,). The second hepatic lipoprotein receptor is the apo-E receptor. It binds apo-E HDLC and chylomicron remnants, but not LDL. The present studies were undertaken to determine whether short-term (acute) regulation of the two receptors can occur in response to perturbations in hepatic cholesterol metabolism. The design used three groups of experimental animals: (a) immature dogs (with both hepatic apo-B,E and apo-E receptors expressed), (b) adult dogs (with predominantly the apo-E receptor expressed and little detectable apo-B,E receptor binding activity), and (c) dogs treated with the bile acid sequestrant cholestyramine or those that have undergone biliary diversion (with apo-E receptors and induced apo-B,E receptors).In per kg) or saline were infused intravenously for 6-8 h into matched pairs of dogs. Serial liver biopsies were obtained at intervals of 1-2 h. A progressive loss of specific (calcium-dependent) binding of LDL was seen in hepatic membranes from both immature and cholestyramine-treated dogs. After 4-6 h of lymph infusion, almost no apo-B,E receptor binding could be detected. The decrease in binding of apo-E HDLC to the same membranes was much less pronounced, and could be explained by a loss of binding of HDLC to the apo-B,E receptor; there was little or no effect on apo-E receptor binding.In the second series of experiments, the effects of a diminished hepatic demand for cholesterol on lipoprotein receptor expression were studied by suppressing bile acid synthesis. The bile acid taurocholate (2-3 jmol/kg per min) was infused intravenously over a 6-h interval. This resulted in a progressive loss of LDL binding to liver membranes of immature or cholestyramine-treated dogs. The infusion of taurocholate for 6 h did not significantly alter the expression of the apo-E receptor binding activity, whereas apo-B,E receptor activity was rapidly down-regulated. Prepara The results indicate that the two canine hepatic lipoprotein receptors differ in their metabolic regulation. The apo-B,E receptor responds rapidly to changes in hepatic requirements for cholesterol. The apo-E receptor appears to be more refractory to acute regulation. The rapidity of the changes in the activity of the apo-B,E receptor (within 2-4 h) suggests that the binding activity of this receptor may be regulated by factors independent of protein synthesis.

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“…This recycling system allows bile acids to circulate 5 to 15 times a day and to exert their major physiological functions in the absorption of dietary lipids, regulation of cholesterol metabolism, solubilization of biliary cholesterol, and bile formation (2)(3)(4)(5)(6)(7). Maintenance of an adequate bile acid pool is dependent upon active absorption by the ileum (8,9), return to the liver in the portal blood bound to albumin (10,11), extraction by hepatic parenchymal cells (12), and secretion against a concentration gradient into the bile canaliculi (13).…”

Section: Introductionmentioning

confidence: 99%