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|Title:||Differential effects of cholestatic and choleretic bile acids on store-operated Ca2+ channels in liver [Abstract]|
|Citation:||Abstracts of the sixty-second annual meeting of the Society of General Physiologists in Journal of General Physiology, 2008; 132(1)|
|Publisher:||Rockefeller University Press|
|Conference Name:||Annual Meeting of the Society of General Physiologists (62 : 2008 : Massachusetts, USA)|
|J.Castro, E.C. Aromantaris, G.J. Barritt and G. Y. Rychkov|
|Abstract:||Cholestasis is a pathological condition of reduced bile formation or flow. It arises from hepatocellular dysfunction, in which bile formation and secretion are impaired, or from intrahepatic or extrahepatic biliary obstruction, in which movement of bile along the biliary tree is impeded. Retention of bile salts within the liver in cholestasis plays a critical role in development and progression of the disease. The more hydrophobic, also called cholestatic bile acids, including taurolithocholate (TLCA) and lithocholate (LCA), amplify the condition by further inhibiting bile flow and causing liver damage. The less hydrophobic bile acids, also called choleretic, including taurodeoxycholate (TDCA) and ursodeoxycholate (UDCA), enhance bile flow and are used to treat some forms of cholestasis. Bile formation, secretion, and flow are largely regulated by Ca2+-mobilizing hormones and intracellular Ca2+. On the other hand, bile salts themselves are known to release Ca2+ from intracellular stores and induce Ca2+ entry. However, the nature of the Ca2+ entry pathways involved is not known. The aim of the present experiments was to identify the Ca2+ channels involved in the actions of choleretic and cholestatic bile acids on hepatocyte [Ca2+]cyt. Using whole cell patch clamping and Ca2+ imaging, we show that TDCA and other choleretic bile acids reversibly activate store-operated Ca2+ channels in liver cells, whereas LCA and other cholestatic bile acids cause their inhibition. The activation of Ca2+ entry by TDCA was observed upon direct addition of the bile acid to the incubation medium, whereas the inhibition by LCA required a 12-h preincubation. TDCA and LCA each caused a redistribution of stromal interaction molecule 1 similar to that induced by thapsigargin, but only TDCA activated Ca2+ entry. It is concluded that physiological and pathological effects of bile salts in the liver involve their actions on store-operated Ca2+ channels|
|Appears in Collections:||Molecular and Biomedical Science publications|
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