Taurocholic Acid (taurocholic + acid)

Distribution by Scientific Domains


Selected Abstracts


Tauroursodeoxycholic acid mobilizes ,-PKC after uptake in human HepG2 hepatoma cells

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2002
Helena Glasova
Abstract Background Tauroursodeoxycholic acid (TUDCA) may exert anticholestatic effects via Ca++ - and ,-protein kinase C (,-PKC)-dependent apical vesicular insertion of canalicular transporters in cholestatic hepatocytes (Hepatology 2001; 33: 1206,16). Tauroursodeoxycholic acid is mainly taken up into liver cells by Na+ -taurocholate cotransporting polypeptide (Ntcp). Tauroursodeoxycholic acid selectively translocates ,-PKC, a key mediator of regulated exocytosis, to hepatocellular membranes. It is unclear whether TUDCA exerts its effects on ,-PKC after carrier-mediated uptake into liver cells or by interaction with extracellular/membraneous structures. Materials and methods Human hepatoblastoma HepG2 cells lacking Ntcp were stably transfected with pcDNA3Ě1/Ntcp or sham-transfected with pcDNA3Ě1 [+]. Distribution of ,-PKC was studied using a Western blotting technique. Uptake of [3H]taurocholic acid (TCA) was determined radiochemically. Results [3H]taurocholic acid uptake was approximately 180-fold higher in Ntcp-transfected than in sham-transfected cells. Phorbol 12-myristate 13-acetate (1 Ámol L,1; positive control) increased membrane binding of ,-PKC by 34% in Ntcp-transfected and by 37% in sham-transfected cells. Tauroursodeoxycholic acid (10 Ámol L,1) increased membrane-associated ,-PKC by 19% in Ntcp-transfected, but not in sham-transfected cells (,13%). Taurocholic acid (10 Ámol L,1) did not affect the distribution of ,-PKC. Conclusion Carrier-mediated uptake is a prerequisite for TUDCA-induced translocation of ,-PKC to hepatocellular membranes. [source]


Taurocholic acid-induced secretion in normal and cystic fibrosis mouse ileum

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2001
J. Hardcastle
Bile acids cause secretion throughout the intestinal tract and this process contributes to maintaining the fluidity of intestinal contents. In cystic fibrosis (CF) defective intestinal secretion can lead to excessive dehydration of the luminal contents and the development of clinical symptoms. This study was designed to investigate bile acid-induced secretion in mouse ileum and to determine whether this process was defective in CF. Taurocholic acid-induced secretion was monitored as a rise in short-circuit current (SCC) in ileal sheets from normal (Swiss MF1) and transgenic CF mice. Taurocholic acid increased the SCC in both intact and stripped ileal sheets from Swiss MF1 mice. This effect was due to a stimulation of electrogenic Cl, secretion as it was inhibited by Cl, -free conditions, serosal furosemide (frusemide), mucosal diphenylamine-2-carboxylic acid (DPC) and increased serosal K+ concentration, without being affected by reduced mucosal Na+ concentration. Taurocholic acid-induced secretion was inhibited by tetrodotoxin, indicating the involvement of a neural pathway, but this did not include capsaicin-sensitive afferent neurons or muscarinic cholinoreceptors. Mucosal mast cells also contributed to the response. Responses in tissues from transgenic wild-type mice were similar to those obtained with Swiss MF1 animals, but ilea from CF mice exhibited a lower basal SCC with significantly reduced secretory responses to acetylcholine and taurocholic acid. We concluded that taurocholic acid induces ileal secretion by a mechanism that entails activation of enteric nerves and degranulation of mucosal mast cells. Impaired bile acid-induced secretion in CF may contribute to luminal dehydration. [source]


Tauroursodeoxycholic acid mobilizes ,-PKC after uptake in human HepG2 hepatoma cells

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2002
Helena Glasova
Abstract Background Tauroursodeoxycholic acid (TUDCA) may exert anticholestatic effects via Ca++ - and ,-protein kinase C (,-PKC)-dependent apical vesicular insertion of canalicular transporters in cholestatic hepatocytes (Hepatology 2001; 33: 1206,16). Tauroursodeoxycholic acid is mainly taken up into liver cells by Na+ -taurocholate cotransporting polypeptide (Ntcp). Tauroursodeoxycholic acid selectively translocates ,-PKC, a key mediator of regulated exocytosis, to hepatocellular membranes. It is unclear whether TUDCA exerts its effects on ,-PKC after carrier-mediated uptake into liver cells or by interaction with extracellular/membraneous structures. Materials and methods Human hepatoblastoma HepG2 cells lacking Ntcp were stably transfected with pcDNA3Ě1/Ntcp or sham-transfected with pcDNA3Ě1 [+]. Distribution of ,-PKC was studied using a Western blotting technique. Uptake of [3H]taurocholic acid (TCA) was determined radiochemically. Results [3H]taurocholic acid uptake was approximately 180-fold higher in Ntcp-transfected than in sham-transfected cells. Phorbol 12-myristate 13-acetate (1 Ámol L,1; positive control) increased membrane binding of ,-PKC by 34% in Ntcp-transfected and by 37% in sham-transfected cells. Tauroursodeoxycholic acid (10 Ámol L,1) increased membrane-associated ,-PKC by 19% in Ntcp-transfected, but not in sham-transfected cells (,13%). Taurocholic acid (10 Ámol L,1) did not affect the distribution of ,-PKC. Conclusion Carrier-mediated uptake is a prerequisite for TUDCA-induced translocation of ,-PKC to hepatocellular membranes. [source]


In vitro determination of active bile acid absorption in small biopsy specimens obtained endoscopically or surgically from the human intestine

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2002
K-A. Ung
Abstract Background In the construction of a Kock reservoir for continent urinary diversion, 70 cm of the distal ileum are used. Impaired absorption of bile acids in these patients might cause diarrhoea. Data on the absorption of bile acids in different parts of the human intestine are limited. Methods Biopsies were taken during endoscopy from the duodenum, the terminal ileum or the right colon, and during surgery 10, 50, 100 and 150 cm proximally to the ileo-caecal valve using standard endoscopy biopsy forceps. The biopsy specimens were incubated in vitro with radio-labelled taurocholic acid at 37 ░C for 22 or 45 min The radioactivity was determined using the liquid scintillation technique. Results A linear increase in the uptake was observed, with increased concentrations of taurocholic acid between 100 and 500 Ám in all specimens tested, that represented passive uptake or unspecific binding. The active uptake could be calculated from the intercept of the line representing passive uptake with the ordinate. The active uptake in the terminal ileum was 3,4 times greater than 100 cm proximal to the valve. Conclusions The active absorption of bile acids in humans can be determined in small biopsy specimens taken using standard biopsy forceps during endoscopy or surgery. This method is suitable for clinical studies of bile acid absorption. Active uptake of bile acids not only takes place in the very distal part of the ileum but also to a considerable degree 100 cm proximally to the ileo-colonic valve. This should be taken into account when selecting the ileal segment for continent urinary diversion. [source]


Taurocholic acid-induced secretion in normal and cystic fibrosis mouse ileum

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2001
J. Hardcastle
Bile acids cause secretion throughout the intestinal tract and this process contributes to maintaining the fluidity of intestinal contents. In cystic fibrosis (CF) defective intestinal secretion can lead to excessive dehydration of the luminal contents and the development of clinical symptoms. This study was designed to investigate bile acid-induced secretion in mouse ileum and to determine whether this process was defective in CF. Taurocholic acid-induced secretion was monitored as a rise in short-circuit current (SCC) in ileal sheets from normal (Swiss MF1) and transgenic CF mice. Taurocholic acid increased the SCC in both intact and stripped ileal sheets from Swiss MF1 mice. This effect was due to a stimulation of electrogenic Cl, secretion as it was inhibited by Cl, -free conditions, serosal furosemide (frusemide), mucosal diphenylamine-2-carboxylic acid (DPC) and increased serosal K+ concentration, without being affected by reduced mucosal Na+ concentration. Taurocholic acid-induced secretion was inhibited by tetrodotoxin, indicating the involvement of a neural pathway, but this did not include capsaicin-sensitive afferent neurons or muscarinic cholinoreceptors. Mucosal mast cells also contributed to the response. Responses in tissues from transgenic wild-type mice were similar to those obtained with Swiss MF1 animals, but ilea from CF mice exhibited a lower basal SCC with significantly reduced secretory responses to acetylcholine and taurocholic acid. We concluded that taurocholic acid induces ileal secretion by a mechanism that entails activation of enteric nerves and degranulation of mucosal mast cells. Impaired bile acid-induced secretion in CF may contribute to luminal dehydration. [source]


Cloning of the dog bile salt export pump (BSEP; ABCB11) and functional comparison with the human and rat proteins

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 8 2008
Hikaru Yabuuchi
Abstract The dog bile salt export pump (BSEP; ABCB11) was cloned and expressed in a Sf9 insect cell system. The deduced amino acid sequence encodes a 1325-amino-acid protein, which shows 89.4% and 80.2% homology with human BSEP and rat Bsep, respectively. The transcript of the dog Bsep gene was detected at a high level in liver, but not other tissues, by quantitative RT-PCR. The BSEP-expressing membrane vesicles isolated from Sf9 cells exhibited saturable uptake of [3H]taurocholic acid with Michaelis constants (Km) of 33.7, 22.2 and 19.9,ÁM for the dog, rat and human transporters, respectively. The uptake of [3H]taurocholic acid by all three transporters was significantly inhibited by troglitazone, glibenclamide, and other several inhibitors, while pravastatin inhibited dog Bsep and human BSEP, but not rat Bsep at 100,ÁM. The IC50 of troglitazone for dog Bsep, human BSEP, and rat Bsep were 32, 20, and 60,ÁM, and those of pravastatin were 441, 240 and >1,000,ÁM, respectively. In conclusion, while dog Bsep shows similar ATP-dependent bile acid transport characteristics to human BSEP and rat Bsep, there is a species difference in affinity for drugs such as pravastatin and troglitazone. Copyright ę 2008 John Wiley & Sons, Ltd. [source]


Effects of bosentan, an endothelin receptor antagonist, on bile salt export pump and multidrug resistance,associated protein 2

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2007
Yuji Mano
Abstract The bile salt export pump (BSEP/Bsep/ABCB11) and multidrug resistance-associated protein 2 (MRP2/Mrp2/ABCC2) are involved in bile acid-dependent and -independent bile secretion, respectively. It has been reported that bosentan, an endothelin receptor antagonist, inhibits Bsep, which may lead to cholestatic liver injury due to the intracellular accumulation of bile salts, while increasing bile salt-independent bile flow. Thus, in this study, the effects of bosentan on BSEP/Bsep and MRP2/Mrp2 were evaluated using membrane vesicles derived from Spodoptera frugiperda (Sf) 9 cells, which express these transporters. The adenosine 5,-triphosphate (ATP)-dependent uptake of 3H-taurocholic acid into membrane vesicles for BSEP/Bsep was inhibited by bosentan, and its IC50 values were 76.8 and 101 ÁM for BSEP and Bsep, respectively. In contrast, bosentan stimulated the MRP2/Mrp2-mediated ATP-dependent vesicular transport of 3H-estradiol 17,-glucuronide by shifting the sigmoidal dependence of transport rate on substrate concentration to a more hyperbolic one. Collectively, these results suggest that bosentan inhibits BSEP in humans with a similar potency to rats, and that increased bile salt-independent flow in rats by bosentan is at least partly attributable to the activation of Mrp2. Copyright ę 2006 John Wiley & Sons, Ltd. [source]