Bile salt-associated electrolyte secretion (original) (raw)
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Effect of sodium taurolithocholate on bile flow and bile acid excretion
Journal of Clinical Investigation, 1968
obstruction of segments of the biliary tree by precipitates of sodium taurolithocholate and possibly to a decrease in water entry into the biliary tree during infusion of this bile acid salt. lanoyl taurine; taurodeoxycholic acid, 3a, 12a,-dihydroxy-5p6-cholanoyl taurine; taurocholic acid, 3a, 7a, 12a-trihydroxy-5j3-cholanoyl taurine; taurocholenic acid, 3fthydroxy-5-cholenoyl taurine; muricholic acids, 3a, 6fl, 7atrihydroxy-5#-cholanoic acid, 3a, 6#3, 7fi-trihydroxy-5#cholanoic acid.
Digestive Diseases and Sciences, 1994
Taurohyodeoxycholic acid is a natural 6et-hydroxylated bile acid with an apparent hydrophilicity intermediate between those of tauroursodeoxycholic and taurocholic acids. We investigated in the rat the hepatobiliary metabolism, choleretic properties, and biliary maximum secretory rate (SRmax) of taurohyodeoxycholic in comparison with these two bile salts. Each compound was infused intravenously, at a rate increased in a stepwise manner from 100 to 300 nmol/min/100 g body wt, in bile salt-depleted bile fistula rats. The three bile salts appeared rapidly starting with the infusion and increased to represent more than 95% of the total bile salts. No apparent biliary metabolites were formed. All the bile salts caused a dose-dependent increase in bile flow and biliary lipid output. The absolute increase in bile flow was lower in rats infused with taurohyodeoxycholic acid, yet the volume of bile formed per nanomole of secreted bile salt was 13.8 nl for taurohyodeoxycholic, 6.4 nl for tauroursodeoxycholic acid, and 10.9 nl for taurocholic. The SRm~, , values were 1080, 3240, and 960 nmol/min/100 g, respectively. At all infusion rates, taurohyodeoxycholic acid caused a greater (P < 0.001) secretion of biliary lecithin compared to the other bile salts. There were no significant differences in the biliary secretion of cholesterol and proteins. Electron microscopy showed the recruitment of vesicles and lamellar bodies around and within bile canaliculi. In conclusion, taurohyodeoxycholic promotes a biliary lecithin secretion greater than expected from physicochemical predictions, representing a novel secretory property with potential pharmacological relevance.
Journal of Hepatology, 1999
Conflicting data on the effects of amino acids on biliary function led us to investigate their interaction with taurocholate in the perfused rat liver model. To investigate the influence of amino acids on the bile acid-independent component of bile flow, 12 livers were perfused with (n = 6) and without (n = 6) amino acid addition from t30 min. For the study of bile acid-dependent bile flow, 24 livers were perfused under 8 experimental conditions according to the perfusate taurocholate concentration (12.5, 25, 37.5 or 50 microM) and whether amino acids were or were not added from t30 min. In the absence of taurocholate, amino acids induced a 40% (p&amp;lt;0.01) decrease in bile flow together with an increase in hepatic water content (17.8%, p&amp;lt; 0.05). Thus, amino acids exert an inhibitory effect on bile acid-independent bile flow despite the postulated cell swelling-dependent increase in bile flow. When livers were perfused at various taurocholate concentrations, amino acids induced, in addition to their inhibitory effect on bile acid-independent bile flow, a significant increase in taurocholate apparent choleretic activity (13.2 microl/micromol vs. 10.6 microl/micromol; p = 0.05), while taurocholate intrinsic clearance was significantly decreased (4.5+/-1.2 ml x min(-1) x g(-1) vs. 6.1+/-1.3 ml x min(-1) x g(-1); p&amp;lt;0.01). These data suggest that at physiological bile acid concentrations amino acids exert an inhibitory effect on both bile acid-dependent and- independent bile flow, whereas at higher taurocholate concentrations this inhibitory effect disappears, probably because of cell swelling-dependent mechanisms.
INFLUENCE OF BILE ACIDS ON THE BILIARY TRANSPORT MAXIMUM OF PHENOLSULPHONPHTHALEIN IN THE RAT
Clinical and Experimental Pharmacology and Physiology, 1988
1. The effect of changes in bile acid secretion induced by cholestyramine treatment or taurocholate infusion on the biliary transport maximum (Tm) of phenolsulfonphthalein (PSP) was studied in Wistar rats. 2. Five hours after oral administration of cholestyramine (1.5 g/kg bodyweight) the biliary output of bile acids decreased to 51% and bile flow to 76% of control values. The percentage of conjugated and unconjugated PSP excreted into bile and the Tm of the dye were not significantly modified by cholestyramine pretreatment. 3. Administration of sodium taurocholate at increasing rates (60-480 nmol/100 g bodyweight per min) enhanced bile flow and the biliary output of bile acids in a linear dose-related fashion. The Tm of PSP increased progressively until a maximum of 29% above the control values was reached at a taurocholate dose of 240 nmol/100 g bodyweight per min). The enhancement corresponded mainly to the unconjugated dye, the excretion of conjugated PSP not being significantly modified by the infusion of the bile acid. 4. The results indicate that bile acids can influence to some extent biliary excretion of PSP in the rat, although this component is of minor importance at low bile acid secretory rates.
Hepatology, 2006
Canalicular bile is modified along bile ducts through reabsorptive and secretory processes regulated by nerves, bile salts, and hormones such as secretin. Secretin stimulates ductular cystic fibrosis transmembrane conductance regulator (CFTR)–dependent Cl− efflux and subsequent biliary HCO3− secretion, possibly via Cl−/HCO3− anion exchange (AE). However, the contribution of secretin to bile regulation in the normal rat, the significance of choleretic bile salts in secretin effects, and the role of Cl−/HCO3− exchange in secretin-stimulated HCO3− secretion all remain unclear. Here, secretin was administered to normal rats with maintained bile acid pool via continuous taurocholate infusion. Bile flow and biliary HCO3− and Cl− excretion were monitored following intrabiliary retrograde fluxes of saline solutions with and without the Cl− channel inhibitor 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) or the Cl−/HCO3− exchange inhibitor 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS). Secretin increased bile flow and biliary excretion of HCO3− and Cl−. Interestingly, secretin effects were not observed in the absence of taurocholate. Whereas secretin effects were all blocked by intrabiliary NPPB, DIDS only inhibited secretin-induced increases in bile flow and HCO3− excretion but not the increased Cl− excretion, revealing a role of biliary Cl−/HCO3− exchange in secretin-induced, bicarbonate-rich choleresis in normal rats. Finally, small hairpin RNA adenoviral constructs were used to demonstrate the involvement of the Na+-independent anion exchanger 2 (AE2) through gene silencing in normal rat cholangiocytes. AE2 gene silencing caused a marked inhibition of unstimulated and secretin-stimulated Cl−/HCO3− exchange. In conclusion, maintenance of the bile acid pool is crucial for secretin to induce bicarbonate-rich choleresis in the normal rat and that this occurs via a chloride–bicarbonate exchange process consistent with AE2 function. (HEPATOLOGY 2006;43:266–275.)