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.

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

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.

Stimulation of ATP secretion in the liver by therapeutic bile acids

2001 ◽  
Vol 358 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Michael H. NATHANSON ◽  
Angela D. BURGSTAHLER ◽  
Anatoly MASYUK ◽  
Nicholas F. LaRUSSO
Keyword(s):  
Bile Acid ◽  
Bile Duct ◽  
Liver Perfusion ◽  
Atp Release ◽  
Rat Hepatocytes ◽  
Therapeutic Benefit ◽  
Isolated Rat Hepatocytes ◽  
Atp Receptors ◽  
Paracrine Signalling ◽  
Isolated Rat

ATP receptors are ubiquitously expressed and are potential targets for the therapy of a number of disorders. However, delivery of ATP or other nucleotides to specific tissues is problematic, and no pharmacological means to stimulate the release of endogenous ATP has been described. We examined the effects of the bile acid ursodeoxycholic acid (UDCA) on ATP release into bile, since this bile acid is the only agent known to be of therapeutic benefit in secretory disorders of the liver, and since its mechanism of action is not established. Both UDCA and its taurine conjugate stimulated secretion of ATP by isolated rat hepatocytes, and produced measurable increases in ATP in bile of isolated rat liver. Perfusion of ATP into microdissected bile-duct segments induced Ca2+ signalling in bile-duct epithelia, while perfusion of bile acid did not. Thus UDCA may promote bile flow by inducing hepatocytes to release ATP into bile, which then stimulates fluid and electrolyte secretion by bile-duct epithelia downstream via changes in cytosolic Ca2+. Moreover, these findings demonstrate the feasibility of using pharmacological means to induce secretion of endogenous ATP. Since the liver and other epithelial organs express luminal ATP receptors, these findings more generally suggest that a mechanism exists for pharmacological activation of this paracrine signalling pathway. This strategy may be useful for treatment of cystic fibrosis and other secretory disorders of the liver and other epithelial tissues.

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