Interaction of fusidates with bile acid uptake by isolated rat hepatocytes

1978 ◽  
Vol 302 (3) ◽  
pp. 329-332 ◽  
Author(s):  
M. S. Anwer ◽  
D. Hegner
Keyword(s):  
Bile Acid ◽  
Rat Hepatocytes ◽  
Acid Uptake ◽  
Isolated Rat Hepatocytes ◽  
Bile Acid Uptake ◽  
Isolated Rat

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.

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.

Transport characteristics of three fluorescent conjugated bile acid analogs in isolated rat hepatocytes and couplets

Hepatology ◽  
1995 ◽  
Vol 22 (2) ◽  
pp. 637-647 ◽  
Author(s):  
Lilia M. Maglova ◽  
Angela M. Jackson ◽  
Xue-Jun Meng ◽  
Michael W. Carruth ◽  
Claudio D. Schteingart ◽  
...  
Keyword(s):  
Bile Acid ◽  
Rat Hepatocytes ◽  
Isolated Rat Hepatocytes ◽  
Isolated Rat

scholarly journals Taurolithocholate and taurolithocholate 3-sulphate exert different effects on cytosolic free Ca2+ concentration in rat hepatocytes

1994 ◽  
Vol 300 (2) ◽  
pp. 383-386 ◽  
Author(s):  
I Marrero ◽  
A Sanchez-Bueno ◽  
P H Cobbold ◽  
C J Dixon
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Rat Hepatocytes ◽  
Signalling Pathway ◽  
Common Mechanism ◽  
Isolated Rat Hepatocytes ◽  
Isolated Rat

Single rat hepatocytes show repetitive oscillations in cytosolic free Ca2+ concentration ([Ca2+]i) when stimulated by agonists acting through the phosphoinositide signalling pathway. We have studied the effect of a natural bile acid, taurolithocholate (TLC), and its sulphated form, taurolithocholate 3-sulphate (TLC-S), on [Ca2+]i in single isolated rat hepatocytes. Although these bile acids are believed to act through a common mechanism to permeabilize the intracellular Ca2+ pool, the [Ca2+]i responses induced by the two compounds were different. Whereas TLC induced a sustained elevation of [Ca2+]i, TLC-S evoked repetitive [Ca2+]i oscillations. In addition, we show that ryanodine, which blocks the Ca(2+)-induced Ca2+ release (‘CICR’) mechanism, blocked TLC-S-induced oscillations in 50% of hepatocytes, but did not affect the TLC-induced rise in [Ca2+]i.

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