SLC10A1 S267F variant influences susceptibility to HBV infection and reduces cholesterol level by impairing bile acid uptake

2019 ◽  
Vol 26 (10) ◽  
pp. 1178-1185 ◽  
Author(s):  
Xiang Cheng ◽  
Ying Wang ◽  
Jianbo Tian ◽  
Li Zhou ◽  
Xueqin Chen ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholesterol Level ◽  
Hbv Infection ◽  
Acid Uptake ◽  
Bile Acid Uptake

cAMP stimulates fluorescent bile acid uptake into hepatocytes by membrane hyperpolarization

1996 ◽  
Vol 270 (2) ◽  
pp. G339-G346 ◽  
Author(s):  
S. Grune ◽  
X. J. Meng ◽  
S. A. Weinman
Keyword(s):  
Bile Acid ◽  
Voltage Clamp ◽  
Uptake Rate ◽  
Direct Consequence ◽  
Acid Uptake ◽  
Net Charge ◽  
Membrane Hyperpolarization ◽  
Whole Cell ◽  
Bile Acid Uptake ◽  
Stimulation Of

Elevation of intracellular adenosine 3',5'-cyclic monophosphate (cAMP) hyperpolarizes hepatocytes and increases the uptake rate of bile acids. The purpose of this study was to determine to what extent these two phenomena are linked. Fluorescent bile acid analogues (FBA) were used to probe bile acid transport into whole cell patch-clamped hepatocytes. Na(+)-dependent uptake of cholyl-nitrobenz-2-oxa-1,3-diazol-4-yl-lysine (C-NBD-L), an FBA with a net charge of -1, was shown to be electrogenic, whereas uptake of cholylglycylamidofluorescein (CGamF), an FBA with a net charge of -2, was neutral. Incubation of hepatocytes with 8-bromo-cAMP (8-BrcAMP; 100 microM) increased the uptake rate of the electrogenically transported FBA by 25% (P = 0.002), but had no effect on the uptake rate of the electroneutrally transported FBA. Microelectrode impalements revealed that 8-BrcAMP or forskolin hyperpolarized hepatocytes by 6-8 mV. To determine if hyperpolarization is responsible for the cAMP-induced increase in uptake rate, cAMP was directly introduced into hepatocytes during whole cell patch clamp under voltage-clamp conditions. As long as voltage clamp was maintained at -30 mV there was no stimulation of C-NBD-L uptake. However, when voltage clamp was terminated by either pipette removal or current clamp, cAMP increased the uptake rate by 25-34% (P < 0.002). In both of these protocols, cAMP had no effect on uptake of the electroneutrally transported FBA, CGamF. Finally, in voltage-clamped hepatocytes in the absence of cAMP, a 10-mV hyperpolarization increased the uptake rate of C-NBD-L by 23%. We therefore conclude that short-term cAMP-induced stimulation of fluorescent bile acid uptake in hepatocytes is a direct consequence of membrane hyperpolarization.

Bile acid uptake by isolated intestinal mucosa cells of guinea pig

1982 ◽  
Vol 721 (3) ◽  
pp. 247-252 ◽  
Author(s):  
Michael Schwenk ◽  
Victor Lopez Del Pino ◽  
Esmail Hegazy
Keyword(s):  
Bile Acid ◽  
Guinea Pig ◽  
Intestinal Mucosa ◽  
Acid Uptake ◽  
Bile Acid Uptake

Effects of gut hormones on bile acid uptake and release in cultured rat hepatocytes

1987 ◽  
Vol 22 (2) ◽  
pp. 174-178 ◽  
Author(s):  
Ichiro Shimizu ◽  
Meisei Hirota ◽  
Mitsuhiro Matsumura ◽  
Kenji Shima
Keyword(s):  
Bile Acid ◽  
Gut Hormones ◽  
Rat Hepatocytes ◽  
Acid Uptake ◽  
Bile Acid Uptake ◽  
Cultured Rat Hepatocytes ◽  
Uptake And Release

Interaction of bumetanide derivatives with hepatocellular bile acid uptake

1993 ◽  
Vol 265 (5) ◽  
pp. G942-G954
Author(s):  
E. Petzinger ◽  
W. Follmann ◽  
M. Blumrich ◽  
R. Schermuly ◽  
S. Schulz ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Model Building ◽  
Organic Anion ◽  
Rat Hepatocytes ◽  
Salt Transport ◽  
Acid Uptake ◽  
Ligand Interaction ◽  
Isolated Rat Hepatocytes ◽  
Bile Acid Uptake

The loop diuretic bumetanide is an organic monocarboxylic organic anion assumed to be transported into hepatocytes by a transport system for bile acids. The structural requirements of 22 bumetanide analogues were analyzed for an interaction with bile acid uptake into isolated rat hepatocytes. Whereas bumetanide inhibited the hepatocellular uptake of [14C]cholate to the same degree as its own uptake, derivatization altered affinity and specificity and yielded compounds that selectively inhibited either cholate or taurocholate uptake or uptake of both. No correlation was found between the diuretic potency of bumetanide derivatives, reflecting the affinity to the Na(+)-K(+)-Cl- cotransporter, and their affinity to hepatic bile salt transport. Computer-aided model building combined with the calculation of potential energy maps showed a strictly amphipathic charge separation in bumetanide analogues as in bile acids. Ranking bumetanide compounds by their mean inhibitory concentration values, inhibition constants, and their type of competition, we conclude that at least three binding domains in the proteins are essential for recognition by bile acid transporters, namely two hydrophobic and an anionic side, and that for the anionic binding region a carbonyl atom in the ligands as an electron donor group is sufficient for ligand interaction.

P1194 : Delayed bile acid uptake with metabolic consequences in NA+-taurocholate cotransporting polypeptide knockout mice

2015 ◽  
Vol 62 ◽  
pp. S803
Author(s):  
D. Slijepcevic ◽  
J.M. Donkers ◽  
C. Kaufman ◽  
C.G.K. Wichers ◽  
E.H. Gilglioni ◽  
...  
Keyword(s):  
Bile Acid ◽  
Knockout Mice ◽  
Acid Uptake ◽  
Bile Acid Uptake

T1869 Bile Acid Uptake Capacity in Ileal Mucosa Correlates With the Expression of Apical but Not Intracellular Bile Acid Transporter

2010 ◽  
Vol 138 (5) ◽  
pp. S-595-S-596
Author(s):  
Antal Bajor ◽  
Anita Fae ◽  
Anders Kilander ◽  
Lena Ohman ◽  
David Pazooki ◽  
...  
Keyword(s):  
Bile Acid ◽  
Acid Uptake ◽  
Uptake Capacity ◽  
Ileal Mucosa ◽  
Bile Acid Uptake ◽  
Bile Acid Transporter ◽  
Acid Transporter

scholarly journals Bile Acid Uptake Transporters as Targets for Therapy

2017 ◽  
Vol 35 (3) ◽  
pp. 251-258 ◽  
Author(s):  
Davor Slijepcevic ◽  
Stan F.J. van de Graaf
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Energy Homeostasis ◽  
Sodium Taurocholate ◽  
Hepatic Uptake ◽  
Farnesoid X Receptor ◽  
Acid Uptake ◽  
Bile Acid Uptake ◽  
Uptake Transporters ◽  
Conjugated Bile Acids

Background: Bile acids are potent signaling molecules that regulate glucose, lipid and energy homeostasis predominantly via the bile acid receptors farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor 5 (TGR5). The sodium taurocholate cotransporting polypeptide (NTCP) and the apical sodium dependent bile acid transporter (ASBT) ensure an effective circulation of (conjugated) bile acids. The modulation of these transport proteins affects bile acid localization, dynamics and signaling. The NTCP-specific pharmacological inhibitor myrcludex B inhibits hepatic uptake of conjugated bile acids. Multiple ASBT-inhibitors are already in clinical trials to inhibit intestinal bile acid uptake. Here, we discuss current insights into the consequences of targeting bile acid uptake transporters on systemic and intestinal bile acid dynamics and discuss the possible therapeutic applications that evolve as a result.

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