Biomedical subjects
Publications and source records attributed to A I Masiuk.
A decrease in the bile flow and bile acids, proteins and lipids secretion in enkephalines infusion into the portal vein was revealed. The bile secretion changes under the effect of enkephaline seem to result from the latter effect upon metabolic processes in hepatocytes.
The intensity of rat's bile secretion under the intraportal infusion of cholic and taurocholic acids has been studied. The results demonstrate that bile acids decrease bile secretion rate under the infusion of these acids in the physiological saline, and increase bile secretion rate under the infusion in saline, with hydrocarbonic ions. Previous treatment by the transcriptional inhibitor actynomycin D affected the development of the hypercholeretic action of the taurocholic acid. The transcriptional activity of the isolated nuclei of liver cells is increased under taurocholic acid action, and decreased under the cholic acid action. The results show that choleretic effects of the bile acids is realised, at least, partially, on the level of the regulatory molecular mechanisms of the cell, the transcription among them.
A process of bile production is considered from molecular physiological point of view. The author summarizes the present-day data available in the literature on the secretion of bile by parenchymatous cells of the liver (hepatocytes); permeability of intrahepatocytic tight junctions for water and electrolytes; hepatocytic excretion of organic and inorganic bile compounds; bile secretion (aqueous solution of electrolytes) by the epithelial cells of the biliary duct, water reabsorption from primary bile in the biliary duct.
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The enhanced bile secretion induced by hydrocortisone coincides in time with activation of the biosynthesis of intracellular and export proteins of the liver. Preliminary inhibition of the protein biosynthesis in the hepatocytes hinders the development of hypercholeretic effects of hydrocortisone or considerably distorts them. The activation of the protein biosynthesis in the liver cells is one of the main molecular mechanisms of choleretic action of glycocorticoids and a number of other hormones.
The bile's proteins were found to be one of the factors regulating the intensity of bile production. Hypocholeresis induced by cycloheximide was followed by suppression of the biosynthesis and secretion of the bile's proteins.
Administration of agents blocking the protein synthesis depressed the liver bile secretion in rats whereas activation of the protein biosynthesis with hydrocortisone increased the bile outflow. The role of different stages of the protein biosynthesis in mechanisms of bile secretion is discussed.
It was shown that rRNA and HnRNA synthesis in rat liver nuclei does not change-within 30 min after intraperitoneal injection of acetylcholine (0.005 mg per 100 g of body weight) but decreases after injection of norepinephrine and epinephrine (0.05 mg per 100 g of body weight). The synthesis of rRNA (but not of HnRNA) increases after injection of hydrocortisone (2,5 mg per 100 g of body weight). The synthesis of HnRNA (but not of rRNA) increases after injection of ACTH1-24 (3 ME per 100 g of body weight) and oxytocin (1 ME per 100 g of body weight). The synthesis of rRNA decreases after injection of propranolol and atropine (0.5 mg per 100 g of body weight). At the same time, the synthesis of HnRNA does not change thereby. The inhibitory effect of propranolol and atropine was corrected by electrostimulation of hypothalamus. The content of cAMP and Ca2+ and the phosphorylation degree of nuclear proteins are increased after stimulation of hypothalamus. The phosphorylation of nuclear proteins is increased by 10(-8)-10(-6) M cAMP. The synthesis of RNA in liver nuclei is increased by 10(-6) M cAMP only after addition of cytosol. In this case the activity of RNA-polymerase II increases in a greater degree than that of RNA-polymerase I + III. It is assumed that the regulatory mechanisms of rRNA and HnRNA synthesis are different. The role of hypothalamus electrostimulation, neurotransmitters, hormones, and cAMP in the mechanisms of RNA synthesis in rat liver nuclei is discussed.
The activity of lactic and malic dehydrogenases was examined in the rat heart after stimulation of the hypothalamus. The activity of LDG and MDG was increased after stimulation of the paraventricular nuclei of the hypothalamus and decreased after stimulation of the ventromedial nuclei. Both effects were abolished by preliminary injection of actinomycin D. This finding suggests an important role of heart cells' genetic apparatus in the neurohormonal regulation of the heart metabolism.
It has been shown that the induction of D-RNA synthesis in rat liver nuclei by electrostimulation of hypothalamus is accompanied by a decrease in chromatin protein synthesis and an increase in phosphorylation and acetylation of chromatin proteins. The decrease of the histone synthesis is mainly due to the decrease of [14C]lysine and [14C]alanine incorporation into histones H1 and H4. The relationship between H1, H2b-H3, H2a and H4 histone fractions remains unchanged. Electrostimulation of hypothalamus increases acetylation of H2a and H4 histone fractions and phosphorylation of all histones with the exception of histone H1.
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Electrostimulation of hypothalamus results in an increase of RNA synthesis of the AU-type in liver cells of intact and adrenalectomized rats. No such effect is observed in the animals with denervated liver. An increase in RNA synthesis is accompanied by an increase in the activities of RNA-polymerases II and III and histone hydrolase and a decrease in the activities of RNAse and DNAse. The mechanisms of the effect of the nervous system on the activities of the nucleic acid metabolism enzymes are discussed.
Electric stimulation of paraventricular hypothalamic nucleus results in intensification of RNA synthesis in rat brain. Content of acid proteins and RNA in liver and brain chromatin of geese changes in the period of sexual activity controlled by hypothalamus. With long introduction of hydrocortisone content of non-histone proteins of chromatine and RNA as well as total content of RNA in rat liver cells increases. These and other facts confirm the supposition that the central nervous system has an influence on the function of organs and tissues by means of genetical apparatus of cells.
Hydrocortisone has been studied for its effect on the bile secretion in rat under normal conditions and malfunction of hormonal induction mechanisms due to specific inhibitors of protein synthesis by actinomycin D, cycloheximide and puromycin. The character of changes in bile flow rate, observed as a response to hydrocortisone injection, depends on the intensity of transcription and translation processes in the rat liver cells.
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The infusion of the protein synthesis inhibitors depressed the liver bile secretion and Na, K-ATPase activity of the hepatocyte plasma membranes in rats. The significance of Na, K-ATPase in the mechanism of bile secretion is discussed.
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