Bile Synthesis Peculiarities following Changes in the Functional State of the Endothelin Receptors

Abstract

Endothelin-1(ET-1) regulates a variety of biochemical processes in liver. However, there is no clear view concerning endothelin receptors participation in the regulation of qualitative and quantitative characteristics of liver secretory function. The purpose of this study is to evaluate the choleretic effect of ET-1 and to determine the role of ЕТ А receptors functional state in mediating the effect of ET-1 on bile and its organic components secretion. Endothelin-1 and BQ-123 (cyclo-Asppro-Val-Leu-Trp) were intraportally injected. Bile flow, bile acid concentration and content, hydroxylation and conjugation coefficients were estimated. The results of this study showed that the secreted bile volume was decreased under the effect of endothelin-1and BQ-123, although this decrease was more prolonged and profound in BQ-123 treated animals. Concentration of taurocholates, glycocholic acid and free bile acids was increased in the endothelin treated rats. When BQ-123 was administered, an increase in glycochenodeoxycholic acid+glycodeoxycholic acid (GCDCA+GDCA) and the taurin-conjugated bile acids concentration was found, whereas the free bile acids concentration altered reversely. Coefficient of hydroxylation was diminished when entholelin receptors were blocked. Activation of endothelin receptors by exogenous endothelin-1 intensified bile acids biosynthesis via "neutral pathway,"involving microsomal oxidation enzymes. The present study concludes that the endothelin receptors blockade eliminated the regulatory function of endogenous endothelin and caused a shift in bile acids synthesis to mitochondrial enzymes through "acidic pathway".