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1. The interference between biliary phospholipid and bilirubin secretion was investigated in rats with bile fistulae, under conditions of normal and maximal bilirubin secretion. The enterohepatic circulation of bile salts was interrupted and the animals received infusions of sodium taurocholate, a micelle-forming physiological bile salt.. 2. Sodium taurocholate infusion (0.19 μmol min−1 100 g−1 body weight) induced an increase in bile flow and phospholipid secretion, while basal bilirubin secretion was not increased.. 3. Bilirubin infusion (0.26 μmol min−1 100 g−1 body weight) induced a decrease in basal and taurocholate-stimulated phospholipid secretion. Biliary mixed micelle formation was presumably altered during bilirubin infusion, although bile taurocholate concentration, taurocholate secretion rate and bile flow were not modified.. 4. When sodium taurocholate was infused during bilirubin-decreased phospholipid secretion, this secretion was restored but maximal biliary bilirubin ...
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To be successful pathogens, bacteria must often restrict the expression of virulence genes to host environments. This requires a physical or chemical marker of the host environment as well as a cognate bacterial system for sensing the presence of a host to appropriately time the activation of virulence. However, there have been remarkably few such signal-sensor pairs identified, and the molecular mechanisms for host-sensing are virtually unknown. By directly applying a reporter strain of Vibrio cholerae, the causative agent of cholera, to a thin layer chromatography (TLC) plate containing mouse intestinal extracts, we found two host signals that activate virulence gene transcription. One of these was revealed to be the bile salt taurocholate. We then show that a set of bile salts cause dimerization of the transmembrane transcription factor TcpP by inducing intermolecular disulfide bonds between cysteine (C)-207 residues in its periplasmic domain. Various genetic and biochemical analyses led us ...
Looking for online definition of sodium taurocholate in the Medical Dictionary? sodium taurocholate explanation free. What is sodium taurocholate? Meaning of sodium taurocholate medical term. What does sodium taurocholate mean?
Recent studies have suggested that the canalicular bile salt transport system of rat liver corresponds to a 100-kDa membrane glycoprotein. In the present study we attempted to functionally reconstitute the 100-kDa protein into artificial proteoliposomes. Canalicular membrane proteins were solubilized with octyl glucoside in the presence of asolectin phospholipids. The extracts were treated with preimmune serum or the 100-kDa protein selectively immunoprecipitated with a polyclonal antiserum. Proteins remaining in the supernatant were then incorporated into proteoliposomes by gel-filtration chromatography. Canalicular proteoliposomes containing the 100-kDa protein exhibited transstimulatable taurocholate uptake that could be inhibited by 4,4-diisothiocyanato-2,2-stilbenedisulfonic acid (DIDS). In contrast, no DIDS-sensitive transstimulatable taurocholate uptake was found in 100-kDa protein-free canalicular proteoliposomes. However, when the immunoprecipitated 100-kDa protein was dissociated ...
Background: The interest in the potential effect of thyromimetics in lowering serum cholesterol is growing. Thyroid hormone actions on lipid metabolism are exerted in the liver and mediated by the T3 receptor TRβ1. The creation of molecules transported into hepatocytes by liver-specific transporters can increase the liver selectivity of thyromimetics. Sodium taurocholate co-transporting polypeptide (NTCP), a solute carrier protein primarily expressed on the basolateral membrane of hepatocytes, is particularly interesting. Objectives: The role of NTCP in the liver preferential uptake of a series of new thyromimetics was analysed. Methods: The compounds to test (KB141, KB5588, KB6628, KB6823, KB3488, KB3493, KB3495, KB4933, KB4956, KB5035, KB5160, KB5359, KB5525, KB5526, KB5866, KB6594, KB8038) were synthesised at Karo Bio AB. To explore the effect of NTCP on the nuclear availability of each compound, COS1 cells were co-transfected with TRβ1, NTCP, a construct coding for a TRE-dependent ...
Gerloff, T., Meier, P. J. and Stieger, B. (1998), Taurocholate induces preferential release of phosphatidylcholine from rat liver canalicular vesicles. Liver, 18: 306-312. doi: 10.1111/j.1600-0676.1998.tb00810.x ...
TY - JOUR. T1 - Bile acid efflux mediated by the rat liver canalicular bile acid transport/ecto-ATPase protein requires serine 503 phosphorylation and is regulated by tyrosine 488 phosphorylation. AU - Sippel, C. Jeffrey. AU - Fallon, Robert J.. AU - Perlmutter, David H.. PY - 1994/7/29. Y1 - 1994/7/29. N2 - Transfection of cDNA for a hepatocyte canalicular phosphoprotein, the rat liver canalicular bile acid transporter/ecto-ATPase/cell CAM 105, confers bile acid efflux and ecto-ATPase activities on heterologous cells (Sippel, C. J., Suchy, F. J., Ananthanarayanan, M., and Perlmutter D. H. (1993) J. Biol. Chem. 268, 2083-2091). Our previous studies have also indicated that there is a positive correlation between the degree of phosphorylation of this transporter and its bile acid efflux activity. In this study, we introduced site-specific mutations of amino acid residues within a protein kinase C- dependent (T502A, S503A) and a tyrosine kinase-dependent (Y488F) phosphorylation consensus sequence ...
The enterohepatic circulation of bile acids is one of the most efficient recycling routes in the human body. It is a complex process involving numerous transport proteins, which serve to transport bile acids from the small intestine into portal circulation, from the portal circulation into the hepatocyte, from the hepatocyte into the bile, and from the gall bladder to the small intestine. The tremendous transport capacity and organ specificity of enterohepatic circulation combined with versatile derivatization possibilities, rigid steroidal backbone, enantiomeric purity, availability, and low cost have made bile acids attractive tools in designing pharmacological hybrid molecules and prodrugs with the view of improving intestinal absorption, increasing the metabolic stability of pharmaceuticals, specifically targeting drugs to organs involved in enterohepatic circulation, as well as sustaining therapeutically reasonable systemic concentrations of active agents. This article briefly describes bile acid
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The Na+-taurocholate cotransporting polypeptide (NTCP) is the predominant transporter responsible for bile acid uptake from portal blood across the basolateral membrane of hepatocytes. In rodent models of cholestasis, expression of the Ntcp mRNA and protein is notably decreased (22, 27, 104). Certain human diseases with a cholestatic component, such as primary biliary cirrhosis and cholestatic alcoholic hepatitis, are also associated with reduced NTCP expression (111, 112). Thus, in addition to enhancing bile acid efflux through induction of BSEP, bile acids suppress the expression of the major bile acid uptake system in conditions of elevated hepatocellular bile acid concentrations. It has been proposed that Fxr-induced Shp is responsible for decreased expression of Ntcp in rats through its interference with the retinoic acid receptor (Rar)-Rxr heterodimer, which has a binding site within the rat Ntcp promoter (16). The Rar-Rxr response element of the rat Ntcp promoter is not conserved in the ...
TY - JOUR. T1 - Importance of cytokines, nitric oxide, and apoptosis in the pathological process of necrotizing pancreatitis in rats. AU - Leindler, László. AU - Morschl, E.. AU - László, F.. AU - Mándi, Y.. AU - Takács, T.. AU - Jármai, Katalin. AU - Farkas, Gyula. PY - 2004/8. Y1 - 2004/8. N2 - Objectives: Ischemia-reperfusion injury can be involved in the pathophysiology of acute necrotizing pancreatitis. The aim of our study was to determine the production of cytokines, tumor necrosis factor (TNF) and interleukin-6 (IL-6), the activation of the inducible nitric oxide synthase (iNOS), and the development of apoptosis during this pathologic process. Methods: Acute pancreatitis was produced in male Wistar rats by injection of 200 μL of 6% taurocholic acid into the main pancreatic duct in combination with the temporary (15 minutes) occlusion of the inferior splenic artery. Six and 24 hours later, the histologic damage was evaluated, and serum amylase, TNF, IL-6 levels, and INOS and ...
Digitalis-like compounds (DLCs) such as digoxin, digitoxin, and ouabain, also known as cardiac glycosides, are among the oldest pharmacological treatments for heart failure. The compounds have a narrow therapeutic window, while at the same time, DLC pharmacokinetics is prone to drug-drug interactions at the transport level. Hepatic transporters organic anion transporting polypeptide (OATP) 1B1, OATP1B3, and Na+-dependent taurocholate co-transporting polypeptide (NTCP) influence the disposition of a variety of drugs by mediating their uptake from blood into hepatocytes. The interaction of digoxin, digitoxin, and ouabain with hepatic uptake transporters has been studied before. However, here, we systematically investigated a much wider range of structurally related DLCs for their capability to inhibit or to be transported by these transporters in order to better understand the relation between the activity and chemical structure of this compound type. We studied the uptake and inhibitory potency ...
Large interindividual differences were found in the level of expressed NTCP mRNA obtained from livers of disease-free donors; the difference in expressed mRNA level between the sample exhibiting the lowest level (HL123, Fig. 1) and the highest (HL104, Fig. 1) was 40-fold. In studies of rats, a 10-fold increase in Ntcp mRNA level after prolactin treatment was associated with a 2-fold increase in theVmax value for taurocholate uptake (Liu et al., 1994). Clearly, the measurement of NTCP protein will be an important next step in delineating whether this large variability in NTCP mRNA levels is similarly reflected at the protein level. However, this is currently difficult to determine because a high-affinity antibody against NTCP is not available.. Recombinant vaccinia-mediated expression of NTCP showed the uptake of taurocholate to be rapid and predominantly sodium dependent (Fig. 2). The derived Km value of 7.9 ± 2.0 μM for taurocholate uptake is in close agreement to theKm value of 6.2 μM ...
We report that, using an experimental model of AP in Wistar rats, diazoxide can reduce necrosis of acinar cells without affecting the overall inflammatory response.. The experimental model used in the present study was effective for AP induction. Sodium taurocholate caused severe histologic damage similar to that observed for other experimental models 14-16. Significant edema, intense infiltration of leukocytes and intra-pancreatic bleeding shows the similarity of the histopathology of experimental lesions with moderate-to-severe pancreatitis in humans 14,15. Mortality in the control group at 24 h was 22%, similar to the mortality (20%) obtained using glycodeoxycholic acid (5-10 mmol) by other research teams. The different mortality obtained in the treatment group could have been related to the effects on blood pressure because this parameter was not controlled in our study.. Despite the anti-inflammatory effect of diazoxide shown in other studies, there was no effect on expression of ...
Summary of Facts and Submissions. I. The appeal of the patent proprietor (appellant) lies against the decision of the opposition division announced at the oral proceedings on 26 November 2009 to revoke European Patent 0 901 786. Independent claims 1 and 21 of the patent as granted read as follows:. 1. A composition comprising a spray dried solid dispersion, which dispersion comprises a sparingly water-soluble drug and HPMCAS wherein the drug to HPMCAS weight ratio is from 1/0.4 to 1/20; said drug being molecularly dispersed and amorphous in said dispersion;. said dispersion satisfying either of the following tests:. (a) providing a maximum concentration of said drug in MFD (model fasted duodenal fluid) that is higher by a factor of at least 1.5 relative to a control composition;. wherein MFD is water which is 82 mM in NaCl, 20 mM in Na2HP04, 47 mM in KH2P04, 14.7 mM in sodium taurocholate and 2.8 mM in 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine to yield a solution pH of about 6.5 and osmotic ...
Background & Aims: Ileal bile acid absorption is mediated by uptake via the apical sodium-dependent bile acid transporter (ASBT), and export via the basolateral heteromeric organic solute transporter α-β (OSTα-OSTβ). In this study, we investigated the cytotoxic effects of enterocyte bile acid stasis in Ostα-/-mice, including the temporal relationship between intestinal injury and initiation of the enterohepatic circulation of bile acids. Methods: Ileal tissue morphometry, histology, markers of cell proliferation, gene, and protein expression were analyzed in male and female wild-type and Ostα-/-mice at postnatal days 5, 10, 15, 20, and 30. Ostα-/-Asbt-/-mice were generated and analyzed. Bile acid activation of intestinal Nrf2-activated pathways was investigated in Drosophila. Results: As early as day 5, Ostα-/-mice showed significantly increased ileal weight per length, decreased villus height, and increased epithelial cell proliferation. This correlated with premature expression of the ...
Background & Aims: Ileal bile acid absorption is mediated by uptake via the apical sodium-dependent bile acid transporter (ASBT), and export via the basolateral heteromeric organic solute transporter α-β (OSTα-OSTβ). In this study, we investigated the cytotoxic effects of enterocyte bile acid stasis in Ostα-/-mice, including the temporal relationship between intestinal injury and initiation of the enterohepatic circulation of bile acids. Methods: Ileal tissue morphometry, histology, markers of cell proliferation, gene, and protein expression were analyzed in male and female wild-type and Ostα-/-mice at postnatal days 5, 10, 15, 20, and 30. Ostα-/-Asbt-/-mice were generated and analyzed. Bile acid activation of intestinal Nrf2-activated pathways was investigated in Drosophila. Results: As early as day 5, Ostα-/-mice showed significantly increased ileal weight per length, decreased villus height, and increased epithelial cell proliferation. This correlated with premature expression of the ...
Animal studies allow for greater understanding of kinetics because more tissues can be sampled and environmental and genetic cialis 20mg factors can be controlled. Apical sodium-dependent bile acid transporter (ASBT) is responsible for the absorption of bile acids from the intestine. Poly-L-arginine (10(-11) to 10(-7) M) induced concentration-dependent endothelium-dependent relaxation in segments of canine coronary arteries incubated with indomethacin.. Glutamate is a major neurotransmitter in the nervous buy cialis system and its activated receptors possess excitatory and inhibitory forms in muscle fibers of invertebrates. Although many small-molecule HDM2 inhibitors have shown potent in vitro activity, only a limited number of compounds have displayed acceptable pharmacokinetic properties for in vivo evaluation.. Widely known as a severe pathogen of bean plants, the bean common mosaic virus (BCMV) has been reported to infect soybeans only sporadically and the involved strains were all found in ...
A Phase 2 Double-blind, Randomized, Placebo-controlled, Dose-finding Study to Evaluate the Safety, Tolerability and Efficacy of Volixibat Potassium, an Apical Sodium-Dependent Bile Acid Transporter Inhibitor (ASBTi) in Adults with Nonalcoholic Steatohepatitis (NASH)
Synonyms for glycocholic acid in Free Thesaurus. Antonyms for glycocholic acid. 92 synonyms for acid: sour, sharp, tart, pungent, biting, acidic, acerbic, acrid, acetic, vinegary, acidulous, acidulated, vinegarish, acerb, sharp, cutting.... What are synonyms for glycocholic acid?
Bile acids are usually found conjugated to glycine or taurine, a derivative of cysteine. Cells require the presence of an active bile acid transporter for uptake of these conjugated derivatives (10). To test whether conjugated bile acids would also activate FXR, we coexpressed the human ileal bile acid transporter (IBAT) with FXR in CV-1 cells (11). FXR was strongly activated by 3 μM of the taurine or glycine conjugates of CDCA, LCA, and DCA (Fig. 2G). Weaker activation was seen with the conjugated forms of CA, and tauro-MCA was inactive (Fig. 2G). These data indicate that FXR can be activated by conjugated bile acids in tissues that express bile acid transporters such as the terminal ileum, liver, and kidney. The relation between the chemical structure of bile acids and their activation of FXR is in close agreement with the reported effects of bile acids on induction of I-BABP expression in Caco-2 cells and inhibition of Cyp7a expression in hepatocytes (3, 12). Coactivator proteins interact ...
Molecular bases for targeting bile acid-cisplatin derivatives Bamet-R2 [cis-diammine-chloro-cholylglycinate-platinum(II)] and Bamet-UD2 [cis-diammine-bisursodeoxycholate-platinum(II)] toward liver cells were investigated. Carriers for bile acids [human Na(+)-taurocholate cotransporting polypeptide (NTCP)], organic anions [organic anion transporting polypeptide (OATP)], and organic cations [organic cation transporter (OCT)] were expressed in Xenopus laevis oocytes (XO) and Chinese hamster ovary (CHO) cells. Drug uptake was measured by flameless atomic absorption of platinum. Rat Oatp1- or rat Ntcp-transfected CHO cells were able to take up Bamets, but not cisplatin, severalfold more efficiently than wild-type cells. This uptake was enhanced by butyrate-induced expression of both carriers. Uptake of both Bamets by Ntcp-transfected CHO cells was stimulated by extracellular sodium. The amount of Bamets, but not cisplatin, taken up by XO was enhanced when expressing OATP-A, OATP-C, NTCP, OCT1, or ...
BioAssay record AID 103636 submitted by ChEMBL: Inhibitory concentration against Lignostilbene alpha beta-dioxygenase (LSD) was determined in 2 mL of 50 mM HCl buffer containing 4 microg enzyme/mL at 30 degree C.
This originally started happening back in September. He has had, maybe 6 since then. This last one was probably the scariest. I ran blood work as well as a thyroid test, and everything...I repeat everything, came back normal. I was hoping we would get an answer from the blood work, we didnt. Now we are onto step two, which is the Bile-Acid Test, it checks his liver function. If this doesnt turn out, we still have a halter test, which checks hearth function, as well as a CT or something of the short to check out his brain to see if it is seizure activity ...
Baylor researchers find apical sodium-dependent bile acid transporter molecule structure contains a mobile unit that transports bile acids.
This work shows that BPD causes major alterations in BA homeostasis. Key findings are that after BPD, 1) BA synthesis markers increase manifold, 2) plasma BAs are high and preferentially unconjugated, and 3) these changes are sustained over time. These findings are in contrast to what happens after RYGB: 4) BA synthesis markers decrease, 5) plasma BA composition shifts to be preferentially conjugated, and 6) these features both return to normal after 1 year.. The implication that BA synthesis increases after BPD, but not RYGB, may explain the formers stronger effect to reduce serum cholesterol (Table 1), although reduced cholesterol absorption likely also plays a role (31). In this regard, BPD mimics some of the effects of blocking intestinal BA absorption through the use of BA sequestrants or inhibitors of apical sodium-dependent bile acid transporter (ASBT). Each of these treatments results in increased conversion of cholesterol into BAs (32,33). These effects are predicted to be due to ...
Effect of bile acids on DNA synthesis by the regenerating liver was investigated in mice in vivo after partial hepatectomy (PH). Radioactivity incorporation into DNA after [14C]thymidine intraperitoneal administration peaked at 48 h after PH. At this time a significant taurocholate-induced dose-dependent reduction in DNA synthesis without changes in total liver radioactivity content was found (half-maximal effect at approximately 0.1 mumol/g body wt). Effect of taurocholate (0.5 mumol/g body wt) was mimicked by chocolate, ursodeoxycholate, deoxycholate, dehydrocholate, tauroursodeoxycholate, taurochenodeoxycholate, and taurodeoxycholate. In contrast, chenodeoxycholate, glycocholate, glycochenodeoxycholate, glycoursodeoxycholate, glycodeoxycholate, 5 beta-cholestane, bromosulfophthalein, and free taurine lacked this effect. No relationship between hydrophobic-hydrophilic balance and inhibitory effect was observed. Analysis by high-performance liquid chromatography indicated that inhibition of ...
For the past year we have employed a mixture of oleic acid and bile salts for the treatment of patients suffering from various forms of gall-bladder disease. The results obtained, which were reported elsewhere15 were gratifying in a large number of cases. We then decided to undertake an experimental study of the choleretic effect of bile salts and of oleic acid with bile salts to ascertain whether oleic acid which has a direct action on the gall-bladder also enhances the well known choleretic effect of bile salts. Theoretically, as will be shown later, it appeared plausible that such would be ...
Results A 61 year-old man with refractory CDI was treated with FMT. He demonstrated a modest improvement in diarrhoea after a first FMT, but an immediate, complete and sustained resolution of symptoms after a second FMT from a different donor (performed two weeks after the first). 16 S rRNA gene sequencing demonstrated a pattern of faecal bacterial communities that closely resembled that of the healthy donors by one week after the second FMT. Faecal LC-MS analysis revealed the patients gut bile acid profile pre-FMT to be enriched sixfold in taurocholic acid (a potent trigger for C. difficile spore germination in vitro). Post-FMT, the patients gut bile acid profile resembled that of healthy donors, with loss of taurocholate and enrichment of secondary bile acids (which are recognised in vitro as inhibitors of C. difficile growth). PCR of bacterial DNA extracted from faeces displayed no detectable BSH genes in the recipient either pre-FMT or by one week following the first FMT, but BSH presence ...
Human hepatic cancer cell lines such as HepG2, Huh7, and HLE cannot get infected with Hepatitis B virus (HBV) due to lack of an HBV receptor(s). Transfection with HBV genome has so far been referred as a tool to mimic HBV infection. However, since sodium taurocholate cotransporting polypeptide (NTCP) was identified as a functional receptor for HBV (Yan et al., 2012), hepatocyte cell lines that were stably transfected with a plasmid for NTCP expression have been used for HBV infection. This protocol is designed for infection with HBV in human hepatocyte cell line HepG2 expressing NTCP (HepG2-hNTCP-C4 cells; Iwamoto et al., 2014) or primary human hepatocytes (PHHs). In this section, we also describe one of the methods for the assessment of HBV infection: Quantification of the intracellular encapsidated HBV DNA.
The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is the major canalicular bile salt export pump in man. Mutations in this gene cause a form of progressive familial intrahepatic cholestases which are a group of inherited disorders with severe cholestatic liver disease from early infancy. [provided by RefSeq, Jul 2008 ...
Background Peroxisome proliferator-activated receptors (PPARs) are ligand activated transcription factors belonging to the nuclear receptor superfamily. PPARs activation has a profound impact on the local immune response with consequences affecting the progression of chronic inflammatory diseases. Relatively little is known on the role of PPAR-β/δ in the regulation of inflammatory responses. The aim of the present study was to evaluate the influence of PPAR-β/δ receptor in a model of edematous pancreatitis induced in mice by administration of cerulein at supramaximal doses, as well as in necrohemorrhagic model induced by intraductal administration of sodium taurocholate (STC). Measurements Mice were treated with cerulein (50 μg/kg) or STC (5%). GW0742 (0.3 mg/kg) was intraperitoneally administered 1 and 6 hours after cerulein injection or was injected 2 hours before STC infusion. The pancreas and exopancreatic organs were carefully removed for microscopic examination. Pancreatic weight, ...
We have demonstrated in vitro the efficacy of the taurine-conjugated dihydroxy bile salts deoxycholate and chenodeoxycholate in solubilizing both cholesterol and phospholipid from hamster liver bile-canalicular and contiguous membranes and from human erythrocyte membrane. On the other hand, the dihydroxy bile salt ursodeoxycholate and the trihydroxy bile salt cholate solubilize much less lipid. The lipid solubilization by the four bile salts correlated well with their hydrophobicity: glycochenodeoxycolate, which is more hydrophobic than the tauro derivative, also solubilized more lipid. All the dihydroxy bile salts have a threshold concentration above which lipid solubilization increases rapidly; this correlates approximately with the critical micellar concentration. The non-micelle-forming bile salt dehydrocholate solubilized no lipid at all up to 32 mM. All the dihydroxy bile acids are much more efficient at solubilizing phospholipid than cholesterol. Cholate does not show such a pronounced ...
Bile acids are steroidal amphipathic molecules derived from the catabolism of cholesterol. They modulate bile flow and lipid secretion, are essential for the absorption of dietary fats and vitamins, and have been implicated in the regulation of all the key enzymes involved in cholesterol homeostasis. Bile acids recirculate through the liver, bile ducts, small intestine and portal vein to form an enterohepatic circuit. They exist as anions at physiological pH and, consequently, require a carrier for transport across the membranes of the enterohepatic tissues. Individual bile acid carriers have now been cloned from several species. Na(+)-dependent transporters that mediate uptake into hepatocytes and reabsorption from the intestine and biliary epithelium and an ATP-dependent transporter that pumps bile acids into bile comprise the classes of transporter that are specific for bile acids. In addition, at least four human and five rat genes that code for Na(+)-independent organic anion carriers with ...
Glycocholic Acid: The glycine conjugate of CHOLIC ACID. It acts as a detergent to solubilize fats for absorption and is itself absorbed.
Multiplicity for the transport of organic anions across the bile canalicular membrane was studied in vivo and in vitro using dibromosulfophthalein (DBSP), [14C]cefodizime, [3H]leukotriene C4 (LTC4) and indocyanine green (ICG) as model compounds in rats. A high concentration of DBSP in plasma reduced the biliary excretion of cefodizime and leukotriene radioactivity to about 15 and 35% of their control values, respectively, but did not affect the excretion of ICG. A high plasma concentration of ICG reduced the excretion of cefodizime to about 60% of the control value, but exerted minimal effect on the excretion of leukotriene radio-activity and DBSP. In vitro, ATP-dependent uptake of LTC4 into the canalicular membrane vesicles was reduced by DBSP, cefodizime and ICG in a dose-dependent manner, with approximate IC50 values of 0.1 microM, 10 microM, and 1 microM, respectively. The hepatic unbound concentration of DBSP sufficient to reduce the excretion of cefodizime, leukotriene radioactivity and ...
Drugs that interfere with bile acid recycling can prevent several aspects of NASH (nonalcoholic steatohepatitis) in mice fed a high-fat diet. The findings suggest that ASBT inhibitors could be a viable clinical strategy to address NASH, an increasingly common liver disease.
A cholesterol-esterifying enzyme which incorporates exogenous fatty acids into cholesterol esters in the presence of ATP and coenzyme A was demonstrated in 15-day-old rat brain. This enzyme was maximally active at pH 7.4 and distinct from the cholesterol-esterifying enzyme reported earlier (Eto and Suzuki, 1971), which has a pH optimum at 5.2 and does not require cofactors. Properties of the two enzymes have been compared. Both the enzymes showed negligible esterification with acetate and were maximally active with oleic acid. The pH 5.2 enzyme esterified desmosterol, lanosterol and cholesterol at about the same rate, while the pH 7.4 enzyme was only 50% as active ith lanosterol as it was with cholesterol and desmosterol. Phosphatidyl serine stimulated the pH 5.2 enzyme but not the pH 7.4 enzyme. Phosphatidyl choline and sodium taurocholate showed no effect on either of the enzymes. Both the enzymes were associated with particulate fractions, but the pH 7.4 enzyme was localized more in the ...
Albireo is developing A3384 to treat bile acid malabsorption disease (BAM), which has no approved treatment options. Learn about the clinical trial and more.
Synonyms: Dipturus kenojei, Raia fusca, Raia kenojei, Raia porosa, Raja cf. porosa, Raja fusca, Raja japonica, Raja karagea, Raja katsukii, Raja kenojei, Raja porosa, Raja tobae, Raja (Okamejei) fusca, Raja (Okamejei) kenojei, Raja (Okamejei) porosa, Raja (Okamejei) porosa ...
Using improved physiological and chemical methods, we have investigated the effects on bile secretion of a high fat diet, of bile salt preparations, and of
Transporters influence the disposition of chemicals within the body by participating in absorption, distribution, and elimination. Transporters of the solute carrier family (SLC) comprise a variety of proteins, including organic cation transporters (OCT) 1 to 3, organic cation/carnitine transporters (OCTN) 1 to 3, organic anion transporters (OAT) 1 to 7, various organic anion transporting polypeptide isoforms, sodium taurocholate cotransporting polypeptide, apical sodium-dependent bile acid transporter, peptide transporters (PEPT) 1 and 2, concentrative nucleoside transporters (CNT) 1 to 3, equilibrative nucleoside transporter (ENT) 1 to 3, and multidrug and toxin extrusion transporters (MATE) 1 and 2, which mediate the uptake (except MATEs) of organic anions and cations as well as peptides and nucleosides. Efflux transporters of the ATP-binding cassette superfamily, such as ATP-binding cassette transporter A1 (ABCA1), multidrug resistance proteins (MDR) 1 and 2, bile salt export pump, multidrug ...
Bile acids are C24 steroids that are derived in the liver from cholesterol and secreted into the intestinal lumen to aid in emulsification of dietary lipids and lipid-soluble vitamins. The indigenous intestinal microflora modify bile acids, producing up to 20 unique bile acid metabolites. The 7α-dehydroxylation of the bile acids is the most physiologically important bile acid biotransformation. All known intestinal bacteria capable of bile acid 7α-dehydroxylation are anaerobic, gram-positive rods of the genera Clostridium and Eubcicterium. Bile acid 7α-dehydroxylating bacteria often contain bile salt hydrolase, which hydrolyzes the peptide bond in taurine-conjugated bile acids to yield a free bile acid and taurine. Taurine is an organosulfonate containing a sulfite moiety. There have been no published reports indicating whether 7α-dehydroxylating bacteria can utilize taurine. Given that taurine and taurine-conjugated bile acids are found at great concentrations in the intestine, the ability to
Author summary The anaerobic, spore-forming bacterium Clostridium difficile (C. difficile) is a prominent pathogen in hospitals worldwide and the leading cause of nosocomial diarrhea. Numerous risk factors are associated with C. difficile infections (CDIs) including: antibiotics, advanced age, vitamin D deficiency, and proton pump inhibitors. Antibiotic use disrupts the intestinal microbiota allowing for C. difficile to colonize, however, why these other risk factors increase CDI incidence is unclear. Notably, deficient intestinal calcium absorption (i.e., increased calcium levels) is associated with these risk factors. In this work, we investigate the role of calcium in C. difficile spore germination. C. difficile spores are the infectious particles and they must become metabolically active (germinate) to cause disease. Here, we show that calcium is required for C. difficile germination, specifically activating the key step of cortex hydrolysis, and that this calcium can be derived from either within
Hepatitis B virus (HBV) infection of hepatocytes begins by binding to its cellular receptor sodium taurocholate cotransporting polypeptide (NTCP), followed by the internalization of viral nucleocapsid into the cytoplasm. The viral relaxed circular (rc) DNA genome in nucleocapsid is transported into the nucleus and converted into covalently closed circular (ccc) DNA to serve as a viral persistence reservoir that is refractory to current antiviral therapies. Host DNA repair enzymes have been speculated to catalyze the conversion of rcDNA to cccDNA, however, the DNA polymerase(s) that fills the gap in the plus strand of rcDNA remains to be determined. Here we conducted targeted genetic screening in combination with chemical inhibition to identify the cellular DNA polymerase(s) responsible for cccDNA formation, and exploited recombinant HBV with capsid coding deficiency which infects HepG2-NTCP cells with similar efficiency of wild-type HBV to assure cccDNA synthesis is exclusively from de novo HBV ...
Stieger, Bruno; Kullak-Ublick, Gerd A (2013). Bile salt Export Pump BSEP (ABCB11): Role in liver physiology and liver disease. In: Ishikawa, T; Kim, R B; König, J. Pharmacogenomics of Human Drug Transporters: Clinical Impacts. Hoboken, NJ, USA: Wiley-Blackwell, 295-309. ...
A number of processes could have contributed to the lower canalicular enzyme activities in diclofenac-treated rats including: 1) redistribution of proteins from the canalicular membrane to other intracellular domains, 2) decreased protein synthesis, or 3) decreased activity as a result of adduct formation. It has been reported that several models of cholestasis are associated with redistribution of canalicular proteins and/or decreased synthesis (Barr and Hubbard, 1993; Stieger et al., 1994; Rost et al., 1999). For example, phalloidin-induced cholestasis in rats causes redistribution of ecto-ATPase, dipeptidylpeptidase IV, and a number of ATP-dependent transporter proteins as a result of disruption and internalization of canalicular membrane fragments (Rost et al., 1999). Bile duct ligation in rats has also been associated with decreased localization of dipeptidylpeptidase IV and ecto-ATPase to canalicular membranes and intracellular accumulation as a result of altered delivery of newly ...
Context Late consequences of acute pancreatitis have received little attention. It is controversial whether the pancreas fully recovers after an episo..