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.

Bile acid transport in cultured rat hepatocytes

1982 ◽  
Vol 243 (6) ◽  
pp. G484-G492 ◽  
Author(s):  
R. W. Van Dyke ◽  
J. E. Stephens ◽  
B. F. Scharschmidt
Keyword(s):  
Bile Acid ◽  
Sodium Chloride ◽  
Lithocholic Acid ◽  
Choline Chloride ◽  
Rat Hepatocytes ◽  
Chloride Cells ◽  
Acid Uptake ◽  
Simple Diffusion ◽  
Bile Acid Uptake ◽  
Uptake Rates

The mechanisms of bile acid uptake have been studied with primary monolayer cultures of rat hepatocytes. Hepatocytes were incubated with taurocholic acid (TC), glycocholic acid (GC), cholic acid (CA), glycochenodeoxycholic acid (GCDC), chenodeoxycholic acid (CDCA), deoxycholic acid (DOCA), lithocholic acid (LCA), or cholylglycylhistamine (CCH), a neutral bile acid derivative for 10 s to 60 min in medium containing sodium chloride, sodium chloride with 1 mM ouabain, or choline chloride. Cells were washed free of radioactive tracer, cell-associated radioactivity was quantitated, and bile acid uptake rates, kinetic parameters of uptake, and steady-state bile acid content were calculated. Two mechanisms for bile acid uptake were identified. Uptake of TC, GC, CA, and GCDC occurred predominantly via a sodium-dependent, ouabain-suppressible saturable mechanism, presumably sodium-coupled transport. Estimates of apparent Km and Vmax for these bile acids were TC, 33 micro M and 0.36 nmol . min-1 . mg prot-1; GC, 18 micro M and 0.22 nmol . min-1 . mg prot-1; CA, 13 micro M and 0.10 nmol . min-1 . mg prot; and GCDC, 6 micro M and 0.21 nmol . min-1 . mg prot, respectively. Uptake via this sodium-coupled mechanism exhibited considerable substrate selectivity. It was enhanced by increased ring hydroxylation and amino acid conjugation and decreased by further conjugation with a neutral histamine group (CGH). In contrast, uptake of CDCA, DOCA, LCA, and CGH occurred primarily via a nonsaturable sodium-independent mechanism, possibly simple diffusion. This mechanism accounted for only a small portion of uptake of TC, GC, CA, and GCDC at low bile acid concentrations. Nonsaturable bile acid uptake rates appeared to correlate with decane-buffer partition coefficients and to be related to bile acid structure.

Amino acid inhibition of bile acid uptake by isolated rat hepatocytes: relationship to dissipation of transmembrane Na+ gradient

1983 ◽  
Vol 245 (3) ◽  
pp. G399-G403
Author(s):  
B. L. Blitzer ◽  
S. L. Ratoosh ◽  
C. B. Donovan
Keyword(s):  
Amino Acids ◽  
Bile Acid ◽  
Amino Acid ◽  
Rat Hepatocytes ◽  
Acid Uptake ◽  
Hepatic Transport ◽  
Transport Pathway ◽  
Isolated Rat Hepatocytes ◽  
Bile Acid Uptake ◽  
Isolated Rat

The effects of amino acids on bile acid uptake were studied in isolated rat hepatocytes. The Na+-dependent amino acid L-alanine inhibited [14C]taurocholate uptake in a nonlinear fashion (IC50, approximately 7 mM). Kinetic studies showed that alanine (30 mM) reduced the Vmax for taurocholate uptake from 1.7 +/- 0.1 to 1.1 +/- 0.1 nmol . mg protein-1 . min-1 but did not significantly affect taurocholate Km (42 +/- 7 vs. 35 +/- 7 microM). Taurocholate uptake was also inhibited by alpha-methylaminoisobutyric acid (which shares a common Na+-dependent transport pathway with alanine but is not metabolized) and by L-glutamine (undergoes Na+-dependent hepatic uptake via a carrier distinct from that for alanine). In contrast, the Na+-independent amino acid 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid had no effect on hepatocyte bile acid uptake. Alanine induced a twofold elevation of intracellular sodium concentration as determined by the steady-state uptake of 22Na. These findings suggest that Na+-dependent amino acids noncompetitively inhibit hepatocyte taurocholate uptake by dissipating the transmembrane Na+ gradient and thereby reduce the driving forces for Na+-coupled bile acid entry. Dissipation of the Na+ gradient by substrates that undergo Na+-dependent hepatic transport may represent a novel mechanism of bile secretory failure.

scholarly journals Bile acid secretion by cultured rat hepatocytes. Regulation by cholesterol availability.

1983 ◽  
Vol 258 (6) ◽  
pp. 3661-3667 ◽  
Author(s):  
R A Davis ◽  
P M Hyde ◽  
J C Kuan ◽  
M Malone-McNeal ◽  
J Archambault-Schexnayder
Keyword(s):  
Bile Acid ◽  
Acid Secretion ◽  
Rat Hepatocytes ◽  
Cultured Rat Hepatocytes ◽  
Bile Acid Secretion
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