Effect of Bile Acids on Calcium Efflux from Isolated Rat Hepatocytes and Perfused Rat Livers

Abstract

Abstract

The changes in intracellular Ca²⁺ concentration ([Ca²⁺]_i) of hepatocytes induced by certain bile acids are biphasic: an initial increase is followed by a more gradual decrease. This latter decline in [Ca²⁺]_i may be due to an efflux of Ca²⁺ across the plasma membrane. This hypothesis was tested by studying the effect of different bile acids on the efflux of ⁴⁵Ca from preloaded rat hepatocytes and isolated perfused rat livers. The following bile acids were studied: cholic (C), ursodeoxycholic (UDC), chenodeoxycholic (CDC), and deoxycholic (DC) acids; their taurine (T) conjugates (TC, TUDC, TCDC, and TDC); and the taurine, sulfate (S), and glucuronide (Glu) derivatives of lithocholic acid (TLC, LS, TLS, and LGIu, respectively). At 0.3 mM, all bile acids except C, TC, TCDC, UDC, and TUDC significantly increased ⁴⁵Ca efflux from preloaded hepatocytes without affecting cell viability. Dose-response studies revealed that the minimum effective concentration needed to induce ⁴⁵Ca efflux was 0.06 mM for LS, 0.8 mM for TCDC, and 10 mM for TC. Efflux of ⁸⁶Rb from preloaded hepatocytes was not significantly altered by 0.1 mM LS, indicating relative specificity for calcium. TDC and DC, but not TC, increased ⁴⁵Ca efflux from preloaded perfused rat livers. These results showed that bile acids known to increase [Ca²⁺]_i, (CDC, DC, TDC, and TLC) also increased ⁴⁵Ca efflux from hepatocytes and perfused livers and that efflux was also stimulated by LS, TLS, and LGlu. The extent of this efflux was related to the hydrophobicity of the steroid nucleus of the bile acid. It is speculated that bile acid-induced increases in [Ca²⁺]_i, activate the plasma membrane Ca²⁺ pump resulting in increased Ca²⁺ efflux.