Inhibitory effects of ammonium ions and some amino acids on stimulated brain respiration and cerebral amino acid transport

1968 ◽  
Vol 46 (6) ◽  
pp. 543-548 ◽  
Author(s):  
S. Nakazawa ◽  
J. H. Quastel
Keyword(s):  
Brain Cortex ◽  
Methionine Sulfoxide ◽  
Respiratory Response ◽  
Inhibitory Effects ◽  
Ammonium Ions ◽  
High Potassium ◽  
Ion Concentrations ◽  
Brain Cortex Slices ◽  
Cortex Slices ◽  
Electrical Impulses

Ammonium ions cause a suppression of the respiratory response of rat brain cortex slices to electrical stimulation and this is partly reversed by the addition of DL-methionine sulfoxide or L-glutamine but not by addition of L-glutamate or DL-α-methylglutamate. Other basic ions, e.g. tetramethylammonium, pyridine, or pyrimidine, at equivalent concentrations are without effect. Ammonium ions have less inhibitory effect on the respiratory response to high potassium ion concentrations than on that due to application of electrical impulses. They also bring about a marked suppression of the rate of glycine uptake into rat brain cortex slices, the effect being much greater with electrically stimulated brain than with unstimulated brain. Methionine sulfoxide diminishes this suppressive effect. They exercise relatively small inhibitory effects on the depressed rate of glycine uptake obtained in the presence of high potassium ion concentrations. The effect of ammonium ions is considered to be partly due to the fall in cell ATP brought about by the operation of glutamine synthetase. The results are consistent with the view that the extent of stimulation of brain respiration due to electrical impulses or to increased concentration of potassium ions is dependent on the cell level of ATP. L-Glutamate, L-glutamine, or γ-aminobutyrate diminishes the suppressive effects of ammonium ions on glycine influx into brain. L-Glutamate, moreover, diminishes the stimulatory effects of electrical stimulation on brain respiration, lesser effects being produced by L-glutamine or γ-aminobutyrate.

EFFECTS OF SODIUM PHENYLPYRUVATE ON AMINO ACID FORMATION IN BRAIN

1965 ◽  
Vol 43 (7) ◽  
pp. 835-840 ◽  
Author(s):  
T. Itoh
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Brain Cortex ◽  
Acid Formation ◽  
Potassium Ions ◽  
Inhibitory Effects ◽  
High Potassium ◽  
Brain Cortex Slices ◽  
Cortex Slices ◽  
Intracellular Labelling

Rat brain cortex slices were incubated with glucose-U-C14 in normal Krebs–Ringer phosphate media and also media 105 mM in potassium ions. Intracellular labelling of amino acids, such as glutamic acid, glutamine, γ-aminobutyric acid, aspartic acid, and alanine, was estimated by radioautography according to the method of Kini and Quastel. The respiration of brain cortex slices was little affected by the presence of phenylpyruvate. However, the formation of these amino acids was strongly suppressed. Moreover, in high-potassium media, the inhibitory effects of phenylpyruvate were greatly magnified. The addition of phenylalanine had no significant effect either on the oxygen consumption or on the amino acid formation when brain cortex slices were incubated with glucose-U-C14.

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.

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.

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

1958 ◽  
Vol 36 (1) ◽  
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.

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

1958 ◽  
Vol 36 (1) ◽  
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.

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

1962 ◽  
Vol 40 (1) ◽  
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.

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