The effects of bile acids on β-adrenoceptors, fluidity, and the extent of lipid peroxidation in rat cardiac membranes

被引:38
|
作者
Gazawi, H
Ljubuncic, P
Cogan, U
Hochgraff, E
Ben-Shachar, D
Bomzon, A
机构
[1] Technion Israel Inst Technol, Bruce Rappaport Fac Med, Dept Pharmacol, IL-31096 Haifa, Israel
[2] Technion Israel Inst Technol, Fac Food Engn & Biotechnol, IL-31096 Haifa, Israel
[3] Rambam Med Ctr, Dept Psychiat, Haifa, Israel
[4] Univ Calgary, Fac Med, Hlth Sci Ctr, Gastrointestinal Res Grp, Calgary, AB, Canada
关键词
bile acids; cardiomyopathy; cholestasis; membrane fluidity; lipid peroxidation; beta-adrenoceptors; reactive oxygen species;
D O I
10.1016/S0006-2952(00)00259-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Bile acids have been proposed as a causative factor for the cardiomyopathy of cholestatic liver disease, since they cause negative inotropism and chronotropism and attenuate cardiac responsiveness to sympathetic stimulation. Bile acids can also modify membrane fluidity and generate reactive oxygen species (ROS). The effects of 10(-6)-10(-3) M deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA) and their taurine conjugates, TDCA and TCDCA, on (1) the binding characteristics of beta-adrenoceptors, (2) membrane fluidity, and (3) the extent of lipid peroxidation in rat cardiac membranes were assessed. The results were compared to the effects of the oxidant, 10(-4)-10(-3) M hydrogen peroxide (H2O2), and the membrane-fluidizing compound, 5 x 10(-5) M 2-(2-methoxyethoxy)ethyl 8-(cis-2-n-octylcyclopropyl)octanoate (A(2)C). Cardiac beta-adrenoceptor density alone was reduced at 10(-4) M bile acid concentration while, at 10(-3) M bile acids, reductions in both receptor density and affinity were seen. At 10(-4) M H2O2, receptor number and affinity were reduced, whereas A(2)C increased receptor affinity without affecting receptor density. Bile acids (10(-3) M) and 10(-4) M H2O2 reduced membrane fluidity. H2O2 caused a concentration-depenclent increase in the extent of lipid peroxidation, whereas the bile acids and A(2)C had no effect. Bile acids (10(-4) M) reduced beta-adrenoceptor density in the absence of variations in membrane fluidity and in the extent of membrane lipid peroxidation. This result suggests that bile acids, at concentrations equivalent to the plasma/serum total or estimated free bile acid concentration may have a possible role in the etiology of cardiomyopathy of cholestatic liver disease. At 10(-3) M bile acid concentration, beta-adrenoceptor number and affinity were adversely affected, accompanied by a decrease in membrane fluidity but without any significant increase in the extent of membrane lipid peroxidation. Although cardiac beta-adrenoceptor density and affinity and membrane fluidity were adversely affected by bile acids, the relevance of these findings tu our understanding of the etiological basis of hepatic cardiomyopathy is questionable, since such concentrations exceeded the highest concentrations seen in the plasma and/or tissues of patients with cholestatic liver disease. (C) 2000 Elsevier Science Inc.
引用
收藏
页码:1623 / 1628
页数:6
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