Voprosy biokhimii mozga最新文献

When phosphate and tyroxine (activators of brain glutaminase) are used in small amounts, a potentiation of their stimulatory effect is observed. Higher concentrations exhibit an opposite effect. Glutamic acid has a strong inhibitory effect on all the activators of glutaminase given separately. The inhibitory effect of glutamate increases on lowering the pH. On the other hand the potentiation observed on adding two stimulators is increased greatly in the presence of glutamate. On the addition of tyroxine to other stimulators a greater potentiation and rise of glutaminase activity are observed. The potentiation, which occurs on the joint addition of phosphate and tyroxine, is raised with the increase of the amount of glutamic acid, while on the contrary on joining phosphate with other stimulators potentiation is reduced. Potentiation is variable and depends on the pH. Preincubation of brain mitochondrial fraction with guanidine chloride inhibits markedly the stimulatory effect of all the stimulators used, but their joint addition almost abolishes the potentiating effect. In the presence of glutamic acid, due to the increase of the cooperative effect between the two stimulators, glutaminase activity is greatly increased and sometimes its inhibitory effect is not even observed. The data obtained indicate that in brain glutamic acid in the presence of phosphate+thyroxine cannot be considered as an inhibitor of glutaminase and that the important factor here is not so much the absolute levels of the activators as their favorable combinations.

It has been previously reported from this laboratory that CABA affects the retention of norepinephrine (NE) and serotonin (5-HT) in rat brain tissue [2, 3, 4]. The addition of GABA (100 mug/ml) to the incubation medium enhances significantly the loss of NE from slices while the loss of 5-HT is, on the contrary, significantly smaller than that observed from slices incubated parallely for the same period. It has also been shown that this effect is observed only in a balanced ionic medium [1]. With the purpose of finding out the importance of Na+ and Cl- ions in the storage of monoamines and in the effect of GABA on this process in the present report we studied the effect of GABA on the loss of NE and 5-HT from slices of rat mesodiencephalic region incubated in media free of Na+ and Cl- ions. The effect of GABA on Na+, K+-ATP-ase activity, an enzyme involved in the active transport of monoamines, was also studied. The results obtained indicate that loss of both NE and 5-HT from slices was significantly enhanced in a Na+-free medium and that on addition of GABA (100 mug/ml) to such a medium no significant changes GABA were noted. In a Cl--free medium loss of NE from slices was enhanced while that of 5-HT was not affected. When GABA was added to such a medium the usual pattern so far observed in our experiments, i.e. an enhancement in the loss of NE from slices, was found to be reversed. The pronounced decrease of NE observed in a Cl--free medium was found to be partially checked by the addition of GABA, the difference observed being statistically significant. Thus, in a Cl--free medium GABA seems to display an effect on NE storage opposite to that observed in a normal medium. Incubation in a Cl--free medium did not induce any noticeable change in the retention of 5-HT in slices. However, when GABA was added to slices incubated in a Cl--free medium, it no more displayed its usual effect, i.e. it did not inhibit the loss of 5-HT from slices. Under the given experimental conditions, GABA added to a balanced ionic medium did not effect Na+,K+-ATP-ase activity. This is in good agreement with previous results from our laboratory [4] where GABA was shown to have no effect on the uptake of NE and 5-HT by slices of rat brain, an active, carrier-mediated process coupled with Na+,K+-ATP-ase activity.

The nucleic acid content of the nuclear fraction of cerebral hemispheres was studied 1, 3, 7, 20 and 90 days after unilateral removal of superior cervical ganglion. The results obtained indicate that the content of nuclear RNA is significantly reduced in the desympathized side 1 day after removal of the ganglion. Seven days after sympathectomy the content of RNA increases, reaching control levels. Beginning from the 20th day it decreases and remains at a low level for 90 days. This decrease is observed on both sides of the brain. The content of nuclear DNA is significantly reduced seven days following removal of superior cervical ganglion. The possible mechanisms of the alterations observed are discussed in connection with changes in correlation of nucleic acids with nuclear proteins.

1. Valine and leucine uptake into mouse brain slices was stimulated by 1 to 4 mM phenobarbital and pentobarbital. Greater concentrations of these two barbiturates inhibited the transport of these amino acids. Barbital, isobarbituric acid, and 5-nitrobarbituric acid had no effect, while amobarbital and secobarbital produced only inhibition of uptake. 2. Transport of glutamate and aspartate was unaffected by phenobarbital concentrations that inhibited uptake of lysine and alpha-aminoisobutyric acid. 3. Changes in the Na+ and K+ content of the slices were not related to stimulation of valine or leucine uptake. 4. There was no concentrative uptake of phenobarbital by brain slices. The partially saturable uptake of pentobarbital was not by active transport, because the uptake increased after heating brain, liver, or kidney slices to 95 degrees for 10 min. 5. This study shows that individual members of a pharmacologically related group may have specific effects on a composite physiological function (amino acid transport) of brain tissue.

Phosphatidic acid, total and individual phospholipids and ethanolamine levels of rat brain and liver are changed considerably following 40 and even more so after 80, days of alcohol intoxication. In brain the content of phosphatidic acid and total and individual phospholipids is increased and that of ethanolamine reduced. In liver exactly the opposite changes take place with the exception of inositol containing phospholipids, which are considerably reduced both in brain and liver. The study of the first stages of phospholipid synthesis showed that during 40 and 80 days of alcohol intoxication activity of enzymes participating in the metabolism of L-alpha-glycerophosphate (glycerokinase, glycerophosphate dehydrogenase) is increased several fold. This brings to the increase of L-alpha-glycerophosphate, the main product of phosphatidogenesis, through activation of its formation by glycerokinase and glycerophosphate dehydrogenase. Inspite of the fact that in liver activity of enzymes taking part in the metabolism of L-alpha-glycerophosphate is considerably increased during chronic alcohol intoxication its level is not raised. This indicates an activation of phosphatidic acid formation from L-alpha-glycerophosphate and the immediate inclusion of phosphatidic acid in the biosynthesis of neutral fats. The data obtained indicate that chronic alcohol intoxication activates biosynthetic processes of phospholipids in brain and accelerates their break down in liver, bringing to the fatty infiltration of liver.

Present concepts of the hydrolytic deamination of adenylic acid through AMP-aminohydrolase of brain and other tissues are discussed. The content of AMP-aminohydrolase of tissues, its intracellular disposition, physico-chemical properties, physiological role and the regulation of its activity are considered. AMP-aminohydrolase of brain is compared with that of other tissues (muscle, liver, kidney, erythrocytes, etc.), and characteristic features of the regulation of its activity in brain tissue is included. The participation of nucleotides, phosphoorganic compounds, hexokinase and some cations in the regulation of AMP-aminohydrolase activity of brain and other tissues are discussed on the basis of the experiments carried out and the data available.