Physiologic Concentrations of Bile Salts Inhibit Rat Hepatic Alkaline Phosphatase but Not the Intestinal Isoenzyme (original) (raw)
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Influence of bile acids on the soluble phosphatidic acid phosphatase in rat liver
Biochemical and Biophysical Research Communications, 1981
Biliary drainage was found to increase soluble phosphatidic acid phosphatase activity in rat liver about two-fold. Treatment with cholestyramine increased the same activity with about 70%. Treatment with I% eholic acid or chanodeoxycholic acid decreased the activity 76% and 93%, respectively.
Hepatology, 2000
We studied the effects of alkaline phosphatase (AP) on the secretory processes of the rat intrahepatic biliary epithelium as well as the role of the intrahepatic biliary epithelium in the uptake and biliary secretion of exogenous AP. The effects of acute and chronic administration of AP on bile secretory parameters were investigated in vivo in normal and bile duct ligated (BDL) rats and in vitro in isolated rat bile duct units (IBDU). In vivo, acute AP administration decreased bile flow and biliary bicarbonate excretion and abolished secretin choleresis in BDL rats but not in normal rats. On the contrary, the AP inhibitor, levamisole, increased in BDL rat bile flow and biliary bicarbonate excretion. In vitro, basal and secretin-stimulated Cl ؊ /HCO 3 ؊ exchanger activity in IBDU was immediately inhibited by AP intraluminal microinjection (apical exposure) but only after a prolonged exposure to the basolateral pole. Levamisole increased the Cl ؊ /HCO 3 ؊ exchanger activity of IBDU. A significant basolateral uptake of AP occurs in IBDU with a progressive transport to the apical domain. AP chronic treatment increased AP and ␥-glutamyltranspeptidase (␥-GT) activities in the intrahepatic bile ducts and hepatocyte canalicular pole, promoted enlargement of bile canaliculi, and decreased bile flow and biliary bicarbonate excretion. In conclusion, the intrahepatic biliary epithelium plays a role in the uptake and biliary secretion of serum AP. AP inhibits the secretory processes of the intrahepatic biliary epithelium and induces features of intrahepatic cholestasis after chronic administration. These findings indicate that AP plays an active role in down-regulating the secretory activi-ties of the intrahepatic biliary epithelium. (HEPATOLOGY 2000;32:174-184.)
Secretion of hepatic and intestinal alkaline phosphatases: Similarities and differences
Clinica Chimica Acta, 1990
The presence of plasma membrane-bound proteins in the serum of mammals has been noted for many years. Examples of such proteins include alkaline phosphatase (liver, bone, intestinal, and placental) [l], 5'-nucleotidase [2], and gamma-glutamyl transferase [3]. The mechanism of attachment of these proteins to the membrane is now fairly clear. Some proteins, e.g. gamma-glutamyl transferase, are attached to the plasma membrane by a hydrophobic transmembrane sequence [4]. Other proteins, including the alkaline phosphatases (AP), are bound by the fatty acid portion of a phosphatidylinositol-glycan anchor [5]. In spite of this information the mechanism for release of these enzymes from the membrane is not known. Moreover, because secretion is stimulated by factors unique to each organ, the mechanism(s) may differ from organ to organ, e.g. liver and intestine.
Bile salt-associated electrolyte secretion
Experimental and Toxicologic Pathology, 1992
The mechanisms involved in bile salt-induced choleresis are poorly known. To give an insight in this physiological process, bile salt-associated electrolyte secretion was studied following relief of a short-term (2 h) biliary .obstruction in the rat, an experimental model that shows an important diminution of bile salt choleretic efficiency. For this purpose, biliary excretion of total bile salts and electrolytes (sodium, chloride and bicarbonate) were studied in such a model during taurocholate infusion at increasing rates. The results showed that bile flow, bile salt output and electrolyte secretion stimulated by taurocholate,administration were decreased in the rats that were subjected to biliary obstruction. Besides, the choleretic efficiency of the excreted bile salts, as estimated by the slope of the regression line of bile flow vs. bile salt output, was diminished by 46 % (p < 0.005). Multiple regression analysis of bile flow vs. bile salt and electrolyte outputs allowed to detect a selective diminution of the fraction of bile flow related to bile salt-associated electrolyte secretion ("secretory fraction" of the choleretic efficiency of bile salts) (3.2 ± 0.3 vs. 2.5 ± 0.2L1mol, p < 0.05) whereas the "osmotic fraction" of the choleretic efficiency of bile salts was not modified by the treatment (5. a ± 0.4 vs. 5.1 ± 0.3 Llmol, p> 0.05). Since both chloride and bicarbonate biliary concentrations in the volume of bile stimulated by taurocholate were reduced by 53 % and 52 % respectively, a role of these anions in the generation of bile salt-induced choleresis was suggested. Possible mechanisms involved in such a process and in its early impairment during cholestasis are discussed.
The Role of Bile Acids in the Human Body and in the Development of Diseases
Molecules
Bile acids are specific and quantitatively important organic components of bile, which are synthesized by hepatocytes from cholesterol and are involved in the osmotic process that ensures the outflow of bile. Bile acids include many varieties of amphipathic acid steroids. These are molecules that play a major role in the digestion of fats and the intestinal absorption of hydrophobic compounds and are also involved in the regulation of many functions of the liver, cholangiocytes, and extrahepatic tissues, acting essentially as hormones. The biological effects are realized through variable membrane or nuclear receptors. Hepatic synthesis, intestinal modifications, intestinal peristalsis and permeability, and receptor activity can affect the quantitative and qualitative bile acids composition significantly leading to extrahepatic pathologies. The complexity of bile acids receptors and the effects of cross-activations makes interpretation of the results of the studies rather difficult. ...
Quarterly journal of experimental physiology (Cambridge, England), 1984
The influence of two different anaesthetics, sodium pentobarbitone and ethyl urethane, on the enhancement of maximal bilirubin and bromosulphthalein (BSP) excretion induced by bile salts was investigated in rabbits. Two micelle-forming (glycodeoxycholate and taurocholate) and one non-micelle-forming (dehydrocholate) bile salts were used. Under urethane anaesthesia the bile flow was lower than with pentobarbitone, and this could be attributed to a smaller bile salt non-dependent fraction of secretion. The effect of bile salts on the maximal excretion of the two organic anions appeared more clearly related to some kind of micelle interaction in rabbits anaesthetized with urethane than in pentobarbitone-anaesthetized animals. Thus, under urethane, infusions of glycodeoxycholate substantially increased the maximal excretion of bilirubin and BSP, taurocholate exerted an intermediate and dehydrocholate only a small effect. Under pentobarbitone, however, the augmenting action of all three ...