Experimental and Clinical Physiology and BiochemistrySerotonin, which is widely known as a neurotransmitter, vasoactive substances and immunomodulator, also regulates the hepato-biliary system activity. Because of the expression of different types of 5HT receptors on liver cells serotonin regulates metabolic process in hepatocytes, in particular it effects on cholesterol metabolism and bile acids formation. Earlier studies have confirmed the serotonin effects on cholates and lipids concentration in blood plasma of different animals. The aim of this study was to determine the effect of serotonin on the bile acids concentrations in the rats bile and its physical and chemical properties.
Using the method of thin layer chromatography concentrations of six cholates fractions (taurocholic acid, taurodeoxycholic and taurochenodeoxycholic acids, glycocholic acid, glycodeoxycholic and glycochenodeoxycholic acids, cholic acid, deoxycholic and chenodeoxycholic acids) were determined in the rats bile (m = 200–270 g, n = 14) collected in acute experiments and the coefficient of conjugation was calculated.
Significant changes in the concentrations of all fractions of bile acids star ting from the first sample after injection of serotonin were observed: the concentrations of conjugated cholates increased and free cholates decreased compared with baseline. Maximum significant increase of taurodeoxycholic and taurochenodeoxycholic acids (11,9 %; p < 0,05), glycocholic acid (14,2 %; p < 0,05), glycodeoxycholic and glycochenodeoxycholic acids (13,4 %; p < 0,05) concentrations were detected in sample N 2 compared with the baseline and it took about 1,5 hours after serotonin application. Taurocholic acid concentration increased in the second (8,6%; p < 0,05) and the fourth half-hour samples (11,2 %; p < 0,05). Concentrations of free cholates significantly decreased compared with the baseline during the whole time of the experiment. The minimum value of cholic acid concentration reached in sample N 5 (27,6 % decrease; p < 0,05), chenodeoxycholic and deoxycholic acids in the fourth half-hour sample (24,8 % decrease; p < 0,05). In contrast, in the control group showed a statistically significant decrease in the concentrations of all fractions of bile acids compared with the baseline. Compared to control significant differences were found in three fractions: glycocholic acid concentration increased by 17,3 % (p < 0,05) in sample N 4, glycodeoxycholic and glycochenodeoxycholic acids increased by 21,5 % (p < 0,05) in sample № 4 and the content of chenodeoxycholic and deoxycholic acids increased starting from sample N 2 and reached maximum in the final sample (70,3 % over control; p < 0,05).
These results may be due to the influence of serotonin on the level of activity of conjugation enzymes or hepatocytes membranes transport systems acting through signaling molecules, second messengers and kinases. Intensive uptake conjugated bile acids led to increase of cholates intracellular concentrations. This led to the inhibition of bile acid synthesis de novo, which was reflected in the gradual decrease of free bile acids concentration in bile samples of rats. It is also worth noting that the increase of the conjugated bile acids level in the rats’ bile under the influence of serotonin helps to maintain its colloidal state, reduce lithogenic and may be an indirect indication of serotonin effects on the detoxification function of the liver. Perspective research is the study of the serotonin action mechanisms on the metabolism cholesterol and bile acids. In particular, it is important to identify the involvement of certain types of receptors for serotonin effects.
Keywords: liver, bile, bile acids, serotonin
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