Effects of Cerebral Stimuli on Adenine Incorporation into Nucleotides and RNA in Brain Slices from the Rat

1972 ◽  
Vol 50 (6) ◽  
pp. 672-683 ◽  
Author(s):  
N. B. Glick ◽  
J. H. Quastel
Keyword(s):  
Brain Tissue ◽  
Incubation Medium ◽  
Rna Synthesis ◽  
Brain Cortex ◽  
Specific Activity ◽  
Brain Slices ◽  
Brain Cortex Slices ◽  
Specific Activities ◽  
Cortex Slices ◽  
The Brain

Comparisons have been made of the rates of incorporation of [8-14C]adenine into RNA and of the specific activities of labelled ATP, in rat brain cortex slices incubated under conditions affecting nucleotide and RNA synthesis.The presence of 50 mM KCl in the incubation medium causes a considerable reduction of the rate of [8-14C]-adenine incorporation into RNA, with no diminution of the specific activity of the cerebral ATP or of the rate of nucleotide formation from adenine. It is inferred that cerebral RNA synthesis is suppressed by 50 mM KCl in the incubation medium.When K+ is omitted from the incubation medium or in the presence of 198 mM NaCl or 5 mM sodium L-glutamate, both the rate of [8-14C]adenine incorporation into RNA and the specific activity of cerebral ATP are diminished to approximately the same extent. This suggests that the process of RNA synthesis in the brain tissue is but little affected either by the increased ceil concentration of Na+ or by the diminished ATP concentration that obtain under these incubation conditions. The process, however, of [8-14C]adenine incorporation into cell nucleotides is markedly suppressed.The presence of protoveratrine (10 μM) causes at least 40% reduction in the rates of [8-14C]adenine incorporation into both RNA and nucleotides with little reduction in the specific activity of the cerebral ATP. The effects of protoveratrine are abolished by tetrodotoxin, indicating that the effects of protoveratrine are confined to the neurons.It is concluded that reductions of the specific activity of cerebral ATP derived from labelled adenine are due to the diminished rates of nucleotide formation from adenine that occur under specific incubation conditions. Such reductions may give rise to the observed diminutions in the rates of incorporation of labelled adenine into RNA. The relatively small fail in the specific activity of isolated ATP after incubation of brain tissue in the presence of protoveratrine is attributed to the localization of the effects of this drug to the neurons, in which the content and specific activity of ATP are suppressed, while those in the glia are undiminished.

Effects of acetylcholine on potassium-induced changes of GABA and taurine uptakes and release in cerebral cortex slices from the rat

1977 ◽  
Vol 55 (3) ◽  
pp. 356-362 ◽  
Author(s):  
A. M. Benjamin ◽  
J. H. Quastel
Keyword(s):  
Brain Cortex ◽  
Brain Slices ◽  
Suppressive Effect ◽  
Endogenous Gaba ◽  
Sodium Gradient ◽  
Brain Cortex Slices ◽  
Cortex Slices ◽  
Induced Changes ◽  
The Brain ◽  
Uptake And Release

Acetylcholine, in presence of eserine, has little or no effect on the potassium-ion-suppressed concentrative uptakes of GABA and taurine by rat brain cortex slices in contrast with its effect on those of L-glutamate, L-aspartate, and glycine. Potassium ions at a concentration of 30 μequiv./ml in the incubation medium has a marked suppressive effect on the uptakes of GABA and taurine when there is no apparent change in the sodium ion content of the brain tissue. It is concluded that some factor, besides the change in sodium gradient, operates in the mechanism of potassium suppression of GABA and taurine uptakes. Acetylcholine diminishes the potassium-evoked release of endogenous GABA and taurine from brain slices. Its action is Ca2+ dependent and is diminished by atropine. Acetylcholine does not affect the potassium-accelerated release of GABA from brain slices previously loaded with this amino acid. The differences in uptake and release phenomena exhibited by GABA and taurine from those of L-glutamate and L-aspartate may be due to differences between the mechanisms, as well as the sites, of cerebral uptake and release of these two groups of amino acids.

EFFECTS OF ALIPHATIC ALCOHOLS AND ALDEHYDES ON THE METABOLISM OF POTASSIUM-STIMULATED RAT BRAIN CORTEX SLICES

1965 ◽  
Vol 43 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Edward Majchrowicz
Keyword(s):  
Rat Brain ◽  
Brain Cortex ◽  
Brain Slices ◽  
Carbon Chain ◽  
Aliphatic Alcohols ◽  
Inhibitory Effects ◽  
Rat Brain Cortex ◽  
Brain Cortex Slices ◽  
Cortex Slices ◽  
The Brain

Aliphatic alcohols and the corresponding aldehydes inhibit the oxidation of glucose-U-C14to C14O2, total respiratory carbon dioxide formation, and oxygen consumption by potassium-stimulated rat brain cortex slices. The inhibitory effects of alcohols increase with the increase of the length of carbon chain, which is similar to the inhibitory effects of alcohols on the metabolism of liver slices. Forty millimolar pentanol and ethanol inhibit C14O2formation by 92% and 17% respectively. However, aliphatic alcohols at a fraction of the concentrations used with brain slices severely suppress C14O2formation, total CO2formation, and incorporation of acetate-1-C14and glucose-U-C14into hepatic lipids and proteins.At low concentrations aldehyde inhibition increases rapidly with the concentration, which is in direct contrast to ethanol or propanol whose inhibitory effects change slightly. Three millimolar propionaldehyde, butyraldehyde, and valeraldehyde are approximately 6 times more inhibitory to C14O2formation than the corresponding alcohols at 20 mM; acetaldehyde (3 mM), on the other hand, is approximately 24 times more inhibitory than 20 mM ethanol. These observations show that aldehydes affect the metabolism of brain slices in a different manner than the corresponding alcohols, which is consistent with the conclusion that there is no enzyme system present in the brain cortex slices responsible for the oxidation of alcohols to aldehydes. In contrast to aliphatic alcohols, the inhibitory effects of aldehydes do not increase with the length of aliphatic carbon chain. Of all alcohols and aldehydes tested, the inhibitions caused by acetaldehyde and valeraldehyde are most severe and approximately equal at equivalent concentrations. Three millimolar acetaldehyde and valeraldehyde suppress C14O2formation by 58% and 53% respectively. The effects of 3 mM propionaldehyde and butyraldehyde (29% and 26% respectively) are also approximately equal but smaller than those of either acetaldehyde or valeraldehyde.The observed inhibitory effects of alcohols on the metabolism of rat brain cortex slices support the suggestion that the site of ethanol inhibition is partly associated with that component of the oxidative system which is dependent on normal functioning of the active transport of sodium across the nerve cell membrane and partly due to acetaldehyde which is conveyed via the blood stream from liver to the brain. Similar deductions may apply to other aliphatic alcohols. The inhibitory effects of aldehydes are consistent with the conclusion that the inhibition depends on the properties of the aldehyde group rather than on the length of carbon chain, although their effects on ion transport across the nerve cell membrane have yet to be reported.

AMINO ACID TRANSPORT IN BRAIN CORTEX SLICES: I. THE RELATION BETWEEN ENERGY PRODUCTION AND THE GLUCOSE-DEPENDENT TRANSPORT OF GLYCINE

1962 ◽  
Vol 40 (11) ◽  
pp. 1575-1590 ◽  
Author(s):  
P. N. Abadom ◽  
P. G. Scholefield
Keyword(s):  
Incubation Medium ◽  
Energy Production ◽  
Brain Cortex ◽  
Ionic Composition ◽  
Metabolic Inhibitors ◽  
Experimental Conditions ◽  
X Irradiation ◽  
Brain Cortex Slices ◽  
Cortex Slices ◽  
Dependent Transport

Incubation of rat brain cortex slices with glycine in the presence of glucose leads to an accumulation of glycine in the slice. The extent of the accumulation is proportional to the level of adenosine triphosphate in the slice under a wide variety of experimental conditions which lead to changes in this level. Such conditions include change in the glucose concentration in the incubation medium, the presence of metabolic inhibitors, addition of uncoupling agents, alteration of the ionic composition of the medium, incubation under anaerobic conditions, addition of glutamate, X-irradiation, the use of rats of various ages, and the presence of adenosine in the incubation medium. The proportionality is apparent from the constancy of a factor, termed the transport quotient, which is obtained by dividing the extent of uptake of glycine by the observed level of nucleotide pyrophosphate present in the slices.

scholarly journals Effects of tetrodotoxin and anaesthetics on brain metabolism and transport during anoxia

1972 ◽  
Vol 126 (4) ◽  
pp. 851-867 ◽  
Author(s):  
R. Shankar ◽  
J. H. Quastel
Keyword(s):  
Action Potentials ◽  
Brain Cortex ◽  
Aerobic Glycolysis ◽  
Rat Kidney ◽  
Brain Slices ◽  
Anaerobic Glycolysis ◽  
High Concentration ◽  
Adult Rats ◽  
Brain Cortex Slices ◽  
Cortex Slices

1. Tetrodotoxin, at concentrations at which it abolishes generation of action potentials in the nervous system, enhances by about 300% the rate of anaerobic glycolysis of brain-cortex slices from adult rats, or from adult and infant guinea pigs. This occurs to a greater extent in Ca2+-deficient incubation media than in Ca2+-rich media. Tetrodotoxin has no accelerative effect on cerebral aerobic glycolysis. 2. Tetrodotoxin does not affect the rate of anaerobic glycolysis of 2-day-old rat brain-cortex slices, nor that of adult rat kidney medulla, nor that of an extract of an acetone-dried powder of brain. 3. Tetrodotoxin does not affect the rate of penetration of glucose into brain slices. 4. Its effect is not apparent if it is added 10min or later after the onset of anoxia. 5. Its effect diminishes as the concentration of K+ in the incubation medium is increased while that of Na+ is decreased. 6. Its salient effect, at the onset of anoxia, is to diminish influx of Na+ into, and efflux of K+ from, the brain slices. 7. Substances that promote cerebral influx of Na+, e.g. protoveratrine, sodium l-glutamate, diminish the accelerative action of tetrodotoxin. 8. It is concluded that tetrodotoxin exerts its effect on anaerobic glycolysis by suppressing, at the onset of anoxia, the generation of action potentials and thereby the accompanying influx of Na+ and efflux of K+. It is suggested that glycolytic stimulation occurs because a rate-limiting step, e.g. operation of pyruvate kinase, is stimulated by K+ and depressed by Na+. 9. Local anaesthetics behave in a manner similar to that of tetrodotoxin in enhancing cerebral anaerobic glycolysis. 10. Sodium Amytal has a marked effect at relatively high concentration. 11. Tetrodotoxin diminishes efflux of amino acids, particularly glutamate and aspartate, at the onset of anoxia.

BIOCHEMICAL STUDIES ON CHLORPROMAZINE: 2. EFFECTS OF CHLORPROMAZINE ON INCORPORATION INTO PROTEINS, AND BREAKDOWN OF GLYCINE-1-C14BY ISOLATED RAT BRAIN CORTEX

1957 ◽  
Vol 35 (1) ◽  
pp. 1145-1150 ◽  
Author(s):  
O. Lindan ◽  
J. H. Quastel ◽  
S. Sved
Keyword(s):  
Rat Brain ◽  
Brain Cortex ◽  
Experimental Conditions ◽  
Rat Brain Cortex ◽  
Brain Cortex Slices ◽  
High Concentrations ◽  
Cortex Slices ◽  
The Given ◽  
The Brain ◽  
Stimulation Of

Glycine is decomposed in rat brain cortex to yield carbon dioxide. This process, in which C14O2is formed from glycine-1-C14, is markedly stimulated by the presence of 10 mM glucose, the rate of production of C14O2being increased at least threefold. The presence of succinate exercises a much smaller stimulation of C14O2formation. The addition of KCl (0.1 M) or of 2,4-dmitrophenol (0.025 mM), whilst stimulating the rate of oxygen uptake, does not increase the rate of C14O2formation from glycine-1-C14. The addition of K+tends to diminish the rate. The process of glycine-1-C14breakdown to C14O2is almost insensitive to chlorpromazine, under the given experimental conditions, until relatively high concentrations (e.g. 0.6 mM) are used. The presence of chlorpromazine, however, brings about an inhibition of the rate of glycine-1-C14incorporation into rat brain cortex proteins, an inhibition of 20% being recorded at a concentration of the drug (0.2 mM) that has little or no effect on the respiration of the brain or on the rate of breakdown of glycine-1-C14into C14O2. Glycine incorporation into brain cortex proteins is a process relatively sensitive to chlorpromazine, the magnitude of inhibition being of the same order as that brought about by amytal at similar concentrations. It is suggested that chlorpromazine brings about its effects by an uncoupling of phosphorylation from oxidation in brain cortex slices.

UPTAKE OF 5-HYDROXYTRYPTOPHAN-3-C14 AND ITS METABOLISM IN RAT BRAIN CORTEX SLICES

1962 ◽  
Vol 40 (1) ◽  
pp. 1439-1448
Author(s):  
J. P. von Wartburg
Keyword(s):  
Monoamine Oxidase ◽  
Synergistic Effect ◽  
Rat Brain ◽  
Brain Cortex ◽  
Brain Slices ◽  
Inhibitory Effect ◽  
Rat Brain Cortex ◽  
Brain Cortex Slices ◽  
Cortex Slices

Rat brain cortex slices were incubated with 5-hydroxytryptophan-3-C14. A method for determination of 5-hydroxytryptamine-C14 and 5-hydroxyindolacetic acid-C14 formed in brain slices is described. Effects of inhibitors of 5-hydroxytryptophan decarboxylase and monoamine oxidase on the metabolic pathway of 5-hydroxytryptophan-3-C14 were measured. α-Methyl dopa (0.33 mM) decreased the level of 5-hydroxyindolacetic acid to a greater amount than that of 5-hydroxytryptamine. Iproniazid (3.3 mM) resulted in an accumulation of 5-hydroxytryptamine and a decrease of 5-hydroxyindolacetic acid formation of 65%. Pheniprazine (0.1 mM) exerted an inhibitory effect on both 5-hydroxytryptophan decarboxylase and monoamine oxidase. Chlorpromazine (0.5 mM) decreased the level of 5-hydroxytryptamine 60% and had a synergistic effect with the inhibition on respiration of brain slices and 5-hydroxytryptophan transport exerted by 0.2 M n-propanol.

DRUG-INDUCED CHANGES IN THE CYTOPLASMIC RIBONUCLEOPROTEIN CONSTITUENTS OF BRAIN TISSUE

1965 ◽  
Vol 43 (7) ◽  
pp. 959-975 ◽  
Author(s):  
J. J. Ghosh ◽  
R. K. Datta ◽  
K. C. Bhattacharyya
Keyword(s):  
Secondary Structure ◽  
Brain Tissue ◽  
Ribosomal Rna ◽  
Brain Cortex ◽  
Macromolecular Structure ◽  
Drug Induced ◽  
Brain Cortex Slices ◽  
Cortex Slices ◽  
The Stability ◽  
Induced Changes

Studies carried out on the properties of isolated ribosomes from drug-treated brain cortex slices indicate that ribosomes from drug-treated tissues are generally more susceptible to breakdown into smaller components such as proteins, nucleic acids, acid-soluble nucleotides, etc. It seems that some factor or factors responsible for the stability of the complex macromolecular structure of ribonucleoproteins of brain tissue are affected as a result of drug treatment. Ribosomal RNA from drug-treated brain tissue has been isolated under standardized conditions and the secondary structures of RNA have been studied by methods involving thermal hyperchromicity and reaction with formaldehyde. This latter study indicates that, during the action of some of these neuropharmacological drugs, the secondary structure of ribosomal RNA of brain tissue is partially lost. The loss in the stability of cytoplasmic ribonucleoproteins in drug-treated brain tissue may partly be due to the disorganization at the level of the secondary structure of the RNA component.

UPTAKE OF 5-HYDROXYTRYPTOPHAN-3-C14 AND ITS METABOLISM IN RAT BRAIN CORTEX SLICES

1962 ◽  
Vol 40 (10) ◽  
pp. 1439-1448 ◽  
Author(s):  
J. P. von Wartburg
Keyword(s):  
Monoamine Oxidase ◽  
Synergistic Effect ◽  
Rat Brain ◽  
Brain Cortex ◽  
Brain Slices ◽  
Inhibitory Effect ◽  
Rat Brain Cortex ◽  
Brain Cortex Slices ◽  
Cortex Slices

Rat brain cortex slices were incubated with 5-hydroxytryptophan-3-C14. A method for determination of 5-hydroxytryptamine-C14 and 5-hydroxyindolacetic acid-C14 formed in brain slices is described. Effects of inhibitors of 5-hydroxytryptophan decarboxylase and monoamine oxidase on the metabolic pathway of 5-hydroxytryptophan-3-C14 were measured. α-Methyl dopa (0.33 mM) decreased the level of 5-hydroxyindolacetic acid to a greater amount than that of 5-hydroxytryptamine. Iproniazid (3.3 mM) resulted in an accumulation of 5-hydroxytryptamine and a decrease of 5-hydroxyindolacetic acid formation of 65%. Pheniprazine (0.1 mM) exerted an inhibitory effect on both 5-hydroxytryptophan decarboxylase and monoamine oxidase. Chlorpromazine (0.5 mM) decreased the level of 5-hydroxytryptamine 60% and had a synergistic effect with the inhibition on respiration of brain slices and 5-hydroxytryptophan transport exerted by 0.2 M n-propanol.

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