THE EFFECT OF HYDROXYLAMINE AND AMINOOXYACETIC ACID ON THE CEREBRAL IN VITRO UTILIZATION OF GLUCOSE, FRUCTOSE, GLUTAMIC ACID, AND γ-AMINOBUTYRIC ACID

1965 ◽  
Vol 43 (7) ◽  
pp. 865-876 ◽  
Author(s):  
Bernard Haber
Keyword(s):  
Glutamic Acid ◽  
Aspartic Acid ◽  
Brain Cortex ◽  
Pyridoxal Phosphate ◽  
Aminobutyric Acid ◽  
Aminooxyacetic Acid ◽  
Inhibitory Effects ◽  
Brain Cortex Slices ◽  
Cortex Slices

The aerobic incubation of rat brain cortex slices leads to rapid incorporation of metabolite carbon from both glucose-U-C14 and fructose-U-C14 into glutamic acid, aspartic acid, glutamine, alanine, and γ-aminobutyric acid (γABA). Use of labeled glutamic acid results in a greater incorporation into aspartic acid, and no labeling of alanine. The incorporation from γABA-1-C14 is lowest, and does not result in labeling of alanine. Both hydroxylamine and aminooxyacetic acid (AOAA) abolish the incorporation of metabolite carbon into γABA and alanine, and diminish that of glutamine, with labeling of aspartic acid diminished with fructose as the substrate. Both inhibitors abolish all amino acid labeling from γABA-1-C14, and exert differing effects on incorporation from glutamic acid, depending on the presence or absence of glucose. The respiration of brain cortex slices is markedly diminished by AOAA and by the higher concentration of hydroxylamine, whereas with fructose 0.5 mM hydroxylamine is also effective. Similar inhibitory effects are observed on the C14O2 production. The inhibitory effects of AOAA on incorporation of metabolite carbon from glucose, the respiration, and the carbon dioxide production are reversed by pyridoxal phosphate, and spectrophotometric data indicate that this is due to complex formation between the vitamin and the inhibitor.

EFFECTS OF ACETYLSALICYLATE AND 2,4-DINITROPHENOL ON METABOLISM AND TRANSPORT IN RAT BRAIN CORTEX IN VITRO

1963 ◽  
Vol 41 (2) ◽  
pp. 435-454 ◽  
Author(s):  
O. Gonda ◽  
J. H. Quastel
Keyword(s):  
Amino Acids ◽  
Rat Brain ◽  
Brain Cortex ◽  
Transport Processes ◽  
Rat Brain Cortex ◽  
High K ◽  
Increased Sensitivity ◽  
Brain Cortex Slices ◽  
Cortex Slices

The effects of acetylsalicylate and of 2,4-dinitrophenol on the metabolism and transport processes of rat brain cortex slices incubated at 37° in glucose–Ringer media under various conditions have been investigated. The following processes are suppressed by acetylsalicylate (5 mM) or dinitrophenol (0.05 mM) to a much greater extent in media containing 105 mM KCl or 10 mM NH4Cl (which stimulate brain respiration) than in normal media:(a) respiration;(b) incorporation of phosphate into ATP and ADP;(c) conversion of creatine to phosphocreatine;(d) uptake of glutamate or of creatine from the medium to the tissue.The two drugs increase the leakage of amino acids from rat brain cortex slices into the medium, the effects being greatest in the presence of 105 mM KCl or 5 mM glutamate or in the absence of glucose. They change the yields of labelled amino acids from labelled glucose or labelled glutamate.Labelled glutamate is converted to labelled aspartate, γ-aminobutyrate and glutamine in rat brain cortex slices, the addition of glucose bringing about increased yields of glutamine and γ-aminobutyrate and a decreased yield of aspartate. The formation of labelled glutamine from either labelled glutamate or from labelled glucose is suppressed by acetylsalicylate or dinitrophenol, the effects being greater in the presence of 105 mM KCl or 10 mM NH4Cl.The increased sensitivity of the stimulated tissue metabolism to the drugs, in the presence of high K+, or of NH4+or of glutamate, is probably explained by the fact that there is a fall, under these conditions, in the tissue phosphocreatine level. There is, therefore, less reserve phosphocreatine to maintain the level of ATP when neuronal oxidative phosphorylation is suppressed by the addition of acetylsalicylate or of dinitrophenol.

ACTIVE TRANSPORT OF ASCORBIC ACID IN ADRENAL CORTEX AND BRAIN CORTEX IN VITRO AND THE EFFECTS OF ACTH AND STEROIDS

1963 ◽  
Vol 41 (1) ◽  
pp. 597-604 ◽  
Author(s):  
Shail K. Sharma ◽  
R. M. Johnstone ◽  
J. H. Quastel
Keyword(s):  
Ascorbic Acid ◽  
Adrenal Cortex ◽  
Active Transport ◽  
Brain Cortex ◽  
Acid Uptake ◽  
Dependent Process ◽  
Brain Cortex Slices ◽  
Cortex Slices ◽  
Energy Dependent

Uptake of ascorbic acid-1-C14in brain cortex and adrenal cortex slices is an energy-dependent process. Concentration ratios (i.e. ratios of tissue ascorbic acid-1-C14to medium ascorbic acid-1-C14) greater than 4 have been obtained with both tissues in vitro. Ouabain as well as 2, 4-dinitrophenol suppresses ascorbic acid uptake into brain cortex slices.ACTH inhibits the uptake of ascorbic acid-1-C14in adrenal cortex, but not in brain cortex slices. The presence of glucose is necessary for the inhibition. Several cortical steroids, as well as adenosine-3′,5′-monophosphate, at small concentrations inhibit the uptake. The results are consistent with the interpretation that ACTH inhibits the uptake of ascorbic acid in the adrenal cortex through the steroids produced in its presence.

Oxidative metabolism of incubated cerebral cortex slices from pyridoxine-deficient kittens

1961 ◽  
Vol 200 (1) ◽  
pp. 34-38 ◽  
Author(s):  
Guy M. McKhann ◽  
Olaf Mickelsen ◽  
Donald B. Tower
Keyword(s):  
Cerebral Cortex ◽  
Oxygen Uptake ◽  
Oxidative Metabolism ◽  
Pyridoxal Phosphate ◽  
In Vitro Study ◽  
Aminobutyric Acid ◽  
Shunt Pathway ◽  
Pyridoxine Deficiency ◽  
Cortex Slices

Pyridoxine deficiency was produced in weanling kittens by dietary means. Clinically, the deficient animals showed failure to gain weight, ataxia, and, if left on the diet, seizures and death. In vitro study of isolated cerebral cortex slices from the deficient animals showed decreased formation of γ-aminobutyric acid and decreased oxygen uptake when glucose was the substrate. Addition of pyridoxal phosphate to the incubation media corrected both of these defects toward the levels found in normal littermate controls. The decreased oxygen uptake was also corrected by the addition of γ-aminobutyric acid to the media. It is suggested that in pyridoxine deficiency, cerebral oxidative metabolism is impaired by blockage of the γ-aminobutyric acid ‘shunt’ pathway at the glutamic decarboxylase step. The role of this shunt pathway in normal neuronal metabolism is discussed.

THE EFFECTS OF ALIPHATIC ALDEHYDES ON THE RESPIRATION OF RAT BRAIN CORTEX SLICES AND RAT BRAIN MITOCHONDRIA

1958 ◽  
Vol 36 (6) ◽  
pp. 531-541 ◽  
Author(s):  
C. T. Beer ◽  
J. H. Quastel
Keyword(s):  
Rat Brain ◽  
Mitochondrial Respiration ◽  
Brain Cortex ◽  
Brain Mitochondria ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Rat Brain Cortex ◽  
Low Concentrations ◽  
Brain Cortex Slices ◽  
Cortex Slices

A study has been made of the effects of acetaldehyde and n-valeric aldehyde on the respiration of rat brain cortex slices in the presence and absence of 0.1 M KCl. Acetaldehyde at low concentrations (1–2 mM) brings about a marked inhibition of potassium-stimulated respiration of brain cortex slices. The inhibition by acetaldehyde occurs at 1/200th the concentration at which ethanol produces the same effects. The stimulation of brain respiration due to potassium ions is abolished by acetaldehyde at concentrations that have no observable effect on the unstimulated respiration. Acetaldehyde and n-valeric aldehyde, at equivalent concentrations, have almost equal inhibitory effects on potassium-stimulated rat brain cortex respiration. The inhibitory effects of the aldehydes do not increase sharply with increase of their concentrations, in contrast to the effects of the corresponding alcohols. The aldehydes, in contrast to the corresponding alcohols, inhibit brain mitochondrial respiration as markedly as they inhibit brain cortex respiration. The inhibitory effect of the aldehyde on mitochondrial respiration with pyruvate as substrate is greater in the presence of small quantities of malate than in the absence of malate. The acetaldehyde inhibition is abolished on the addition of DPN. The results obtained with the aldehydes do not support the view that the corresponding alcohols exercise their inhibitive effects on brain respiration by preliminary conversion to the aldehydes. It is suggested that the aldehydes exercise their inhibitory effects on brain respiration by rapid attainment of equilibrium with a constituent of the brain respiratory system associated with a rate-limiting step in the citric acid cycle.

AMINO ACID TRANSPORT IN BRAIN CORTEX SLICES: II. COMPETITION BETWEEN AMINO ACIDS

1962 ◽  
Vol 40 (11) ◽  
pp. 1591-1602 ◽  
Author(s):  
P. N. Abadom ◽  
P. G. Scholefield
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Rat Brain ◽  
Amino Acid Transport ◽  
Brain Cortex ◽  
Transport Systems ◽  
Acid Transport ◽  
Inhibitory Effects ◽  
Brain Cortex Slices ◽  
Cortex Slices

Evidence is presented which indicates that several amino acid transport systems are present in rat brain cortex slices, each with its own specificity with regard to substrate and with regard to amino acids which produce inhibitory effects. The nature of these inhibitory effects may be either direct (competition for a limiting number of sites) or indirect (as they are when glutamate or aspartate cause a decrease in the ATP content).Comparison of the specificities of the glycine transport systems present in rat brain cortex slices and in Ehrlich ascites carcinoma cells indicates that these two systems have little in common and the relation of this finding to the structural requirements necessary for chemotherapeutic activity is discussed.

THE EFFECTS OF ALIPHATIC ALCOHOLS ON THE RESPIRATION OF RAT BRAIN CORTEX SLICES AND RAT BRAIN MITOCHONDRIA

1958 ◽  
Vol 36 (6) ◽  
pp. 543-556 ◽  
Author(s):  
C. T. Beer ◽  
J. H. Quastel
Keyword(s):  
Rat Brain ◽  
Brain Cortex ◽  
Brain Mitochondria ◽  
Carbon Chain ◽  
Brain Cell ◽  
Aliphatic Alcohols ◽  
Inhibitory Effects ◽  
Rat Brain Cortex ◽  
Brain Cortex Slices ◽  
Cortex Slices

A study has been made of the effects of a series of aliphatic alcohols (ethanol, n-propanol, isopropanol, n-butanol, and n-pentanol) on the respiration of rat brain cortex slices in the presence or absence of 0.1 M KCl. The respiration of rat brain cortex slices incubated in presence of 0.1 M KCl is found to be much more sensitive to the alcohols than that of the tissue incubated in absence of the added potassium ions. The inhibitory effects of the alcohols increase markedly as the length of the carbon chain increases and with increase of their concentrations. The stimulation of brain cortex respiration by addition of 0.1 M KCl is diminished or abolished by concentrations of the alcohols that have little effect on the unstimulated respiration. n-Pentanol is far more effective than ethanol in effecting an inhibition of potassium-stimulated brain cortex respiration. The inhibitive effects of the alcohols at low concentration on potassium-stimulated brain cortex respiration are not due to a gradual denaturation of tissue proteins. The data point to a rapid establishment of equilibria between the alcohols and components influencing brain respiratory systems. Brain mitochondrial respiration is relatively insensitive to concentrations of alcohols that considerably depress potassium-stimulated respiration of rat brain cortex slices. It is suggested that the alcohols exercise their inhibitory effects on brain cortex respiration at the brain cell membranes.

ACTIVE TRANSPORT OF ASCORBIC ACID IN ADRENAL CORTEX AND BRAIN CORTEX IN VITRO AND THE EFFECTS OF ACTH AND STEROIDS

1963 ◽  
Vol 41 (3) ◽  
pp. 597-604 ◽  
Author(s):  
Shail K. Sharma ◽  
R. M. Johnstone ◽  
J. H. Quastel
Keyword(s):  
Ascorbic Acid ◽  
Adrenal Cortex ◽  
Active Transport ◽  
Brain Cortex ◽  
Acid Uptake ◽  
Dependent Process ◽  
Brain Cortex Slices ◽  
Cortex Slices ◽  
Energy Dependent

Uptake of ascorbic acid-1-C14in brain cortex and adrenal cortex slices is an energy-dependent process. Concentration ratios (i.e. ratios of tissue ascorbic acid-1-C14to medium ascorbic acid-1-C14) greater than 4 have been obtained with both tissues in vitro. Ouabain as well as 2, 4-dinitrophenol suppresses ascorbic acid uptake into brain cortex slices.ACTH inhibits the uptake of ascorbic acid-1-C14in adrenal cortex, but not in brain cortex slices. The presence of glucose is necessary for the inhibition. Several cortical steroids, as well as adenosine-3′,5′-monophosphate, at small concentrations inhibit the uptake. The results are consistent with the interpretation that ACTH inhibits the uptake of ascorbic acid in the adrenal cortex through the steroids produced in its presence.

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.

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