[Effect of nicotinamide adenine dinucleotide on the serotoninergic mediator system in the rat brain during 3-acetylpyridine administration]. / Deistvie nikotinamidadenindinukleotida na serotoninergicheskuiu mediatornuiu sistemu pri vvedenii 3-atsetilpiridina v golovnom mozge krys.

The effect of administration of 3-acetylpyridine (antivitamin B3), on rat brain serotoninergic and NAD receptor systems was investigated. The injection of 3-acetylpyridine to rats caused a decrease of NAD and serotonin content in the brain and changes in [U-14C]NAD binding to synaptic membranes, serotonin uptake by nerve endings, as well as sensitivity of this process to NAD (10-5 M). Pretreatment of animals with nicotinamide restored modulating effect of NAD.

[Role of aldose reductase inhibitors in the development of peripheral neuropathy in experimental diabetes]. / Rol' ingibitorov al'dozoreduktazy v razvitii perifericheskikh neiropatii pri éksperimental'nom diabete.

Streptozotocin-induced diabetes in rats is accompanied by development of diabetic complications such as neuropathies. It was shown that aldose reductase inhibitors (A1-1576, sorbinil and unithiol) administration partially normalized not only polyol pathway. Aldose reductase inhibitors partially restored Na+, K(+)-ATP-ase activity in sciatic nerve of diabetic rats and redox state of nicotinamide adenine dinucleotides. The sorbitol level increases in streptozotocin-diabetic rats as compared to control. Administration of aldose reductase inhibitors to diabetic rats is accompanied by partial reduction of sorbitol level in sciatic nerve. The results obtained confirm the important role of a dose reductase inhibitors, as antidiabetic drugs, in the improvement of diabetic neuropathy.

[Role of nicotinic acid and its derivatives in disorders of nervous system function]. / Rol' nikotinovoi kisloty i ee proizvodnykh pri narusheniiakh funktsii nervnoi sistemy.

Participation of nicotinic acid and its derivates in the functioning of nervous system is considered basing on the data from literature. It is supposed that the favourable therapeutic effects of nicotinamide, nicotinic acid and their active biological form--NAD are realized due to the mechanisms of their functioning in the nervous system, for treating schizophrenia, epilepsy and other diseases of the nervous system.

[The functional characteristics of the inhibitory mediator systems in the brain synaptosomes of PP vitamin-deficient rats]. / Osobennosti funktsionirovaniia tormoznykh mediatornykh sistem sinaptosom golovnogo mozga u PP-gipovitaminoznykh krys.

A decrease of the NAD and serotonin level in the brain of rats with PP hypovitaminosis is shown. NAD in concentration of 10(-6) M in vitro exerts a less pronounced inhibiting influence on the neuronal uptake of [14C]serotonin and [14C]GABA by brain synaptosomes of rats with PP hypovitaminosis. GABA content under such conditions increases as compared with the control and correlates with changes in the [14C]GABA uptake system.

[Functional-metabolic changes in the brain during various conditions of supplying the rat with vitamin PP]. / Funktsional'no-metabolishcekie izmeneniia v mozge pri razlichnoi obespechennosti organizma krys vitaminom PP.

Content of nicotinamide nucleotides, reception of NAD by synaptic membranes and the system of 14C-serotonin uptake and liberation in rat brain nerve endings were studied under various conditions of vitamin PP consumption. In PP hypovitaminosis binding of 14C-NAD was decreased in synaptic membranes as a result of alterations in capacity of receptor sites, which occurred simultaneously with low level of nicotinamide coenzymes in rat brain. These alterations led to deterioration of NAD modulating function in liberation of 14C-serotonin from synaptosomes. The data obtained suggest that functional activity of NAD-receptor system in synaptic membranes of rat brain depends on the rate of vitamin PP consumption. These results might be considered in clinical research when vitamin PP is used for treatment of various diseases.

[Solubilization and various properties of NAD-binding receptor protein from rat brain synaptic membranes]. / Soliubilizatsiia i izuchenie nekotorykh svoistv NAD-sviazyvaiushchego retseptornogo belka sinapticheskikh membran mozga krys.

The NAD-binding receptor protein has been solubilized from the synaptic membranes of the rat brain by different detergents. Digitanin proved to be the most effective detergent which exerted no action on the specific binding of [14C]NAD with the solubilized receptor protein. Kinetic parameters of the soluble ligand-receptor complex were studied. The affinity of the solubilized receptor protein to NAD did not change as compared to the protein of native membranes. The specific binding of [14C]NAD was saturated at Kd = 0.53 microM, Bmax = 0.011 nmol per 1 mg of protein. The molecular weight of the soluble NAD-receptor complex determined under native conditions was equal to 115 kDa.

[Properties of NAD binding by synaptic membranes of rat brain]. / Osobennosti sviazyvaniia NAD sinapticheskimi membranami golovnogo mozga krys.

The binding of [14C]NAD to rat brain synaptic membranes is reversible and depends on incubation time, temperature and protein concentration in the reaction mixture. The value of the rate constant for [14C]NAD binding to the synaptic membranes at 24 degrees C (kl) is 1.1 X 10(-6) M-1 S-1, the rate constant for dissociation of the [14C]NAD-receptor complex (k-1) is 3.3 X 10(-3) S-1. The value of the constant for the ligand dissociation from this complex (Kd) is 3.0 nmole. Treatment of the experimental results in the Scatchard plots for the equilibrium binding of [14C]NAD to the synaptic membranes demonstrated that the receptor sites with high and low affinities for the ligand (Kd1 = 3.3 nmol, Kd2 = 14.4 nmole) and with binding capacities of 44 and 77 pmole of [14C]NAD, respectively. It was found that the synaptosomal membrane components which bind the labelled NAD have a protein nature. Data from [14C]NAD and [nicotinamide-3H]NAD binding suggest that brain synaptic membranes bind NAD at the nicotinamide and adenylic moieties.

[Hypoglycemic effect of nicotinamide in rats with alloxan diabetes]. / Gipoglikemicheskii effekt nikotinamida pri alloksanovom diabete u krys.

Experimentally-induced alloxan diabetes was characterized in rats by a marked increase in the blood glucose level and by a number of disturbances in the concentration of metabolites and the activity of the enzymes of carbohydrate metabolism in the liver. Stimulation of gluconeogenesis in diabetes was judged by reduction of the redox condition of free NAD- and NADP-couples, by the increase in the concentration of phosphoenolpyruvate, malic oxaloacetate and phosphoenolpyruvate carboxykinase activity of the liver. Nicotinamide in a dose of 50 mg per 100 g of body weight caused a marked reduction in the blood glucose level of diabetic rats. An increase of the [NAD+]/[NADN], [NADP+]/[NADPN] ratio, a reduction of the concentration of phosphoenolpyruvate, malate and phosphoenolpyruvate carboxylase activity pointed to the inhibition of gluconeogenesis and stimulation of glycolysis in the liver of diabetic rats given nicotinamide.

[Gluconeogenesis in the liver of rats receiving 1,3-butanediol in their diet]. / Gliukoneogenez v pecheni krys, poluchavshikh v sostave diety 1,3-butandiol.

Inclusion of 1,3-butandiol as a synthetic source of nutritional energy into the composition of a low-carbohydrate diet produced a fall in the ration of free [NAD+]:[NADN] and [NADP]:[NADPN] calculated for the cytoplasm and mitochondria of the liver cell in rats according to the concentration of oxidated and reduced metabolites and the equilibrium constant of the lactate-dehydrogenase, glutamate-dehydrogenase and malic-fermentative systems. In these conditions the concentration of metabolites, at whose level the conjugation of the carbohydrates decomposition during glycolysis and their synthesis at the time of gluconeogenesis (phosphoenol-pyruvate, malate, oxaloacetate) is realized, as well as the activity of key gluconeogenesis enzymes (phosphoenol-pyruvate carboxykinase, fructose-1,6-diphosphatase) increase. The NADN generation in the course of oxidative metabolism of 1,3-butandiol gives rise to reducing properties of the free NAD-par cytoplasm and mitochondria pool, which leads to the intensification of gluconeogenesis in the liver, attended by a drop of the phosphate potential level.

[Role of the oxidation-reduction state and phosphate potential in regulating rat liver gluconeogenesis during inclusion of 1,3-butanediol in the diet]. / Rol' okislitel'no-vosstanovitel'nogo sostoianiia i fosfatnogo potentsiala v reguliatsii gliukoneogeneza v pecheni krys pr vkliuchenii v dietu, 1,3-butandiola.

Gluconeogenesis was stimulated in rat liver tissues if 38.5% of carbohydrates were substituted in the diet by 1,3-butane diol used as a source of energy. Under these conditions concentration of substrates (phosphoenol pyruvate, malate, oxalacetate), participating in coupling of glycolysis and gluconeogenesis, was increased in liver tissue; activity of gluconeogenesis key enzymes (phosphoenolpyruvate carboxykinase and fructose-1,6-diphosphatase) was also increased. Decrease in the ratio NAD+/NADH showed that the nicotinamide nucleotide pool acquired the most distinct reducing properties of cytoplasma and mitochondria of rats maintained on the diet. The value of phosphate potential (the ration ATP/ADP/Pn) was decreased during the experiment due to increase of ATP utilization in gluconeogenesis.