EFFECTS OF SODIUM PHENYLPYRUVATE ON AMINO ACID FORMATION IN BRAIN

1965 ◽  
Vol 43 (7) ◽  
pp. 835-840 ◽  
Author(s):  
T. Itoh

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.

1962 ◽  
Vol 40 (11) ◽  
pp. 1591-1602 ◽  
Author(s):  
P. N. Abadom ◽  
P. G. Scholefield

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.


1977 ◽  
Vol 55 (3) ◽  
pp. 347-355 ◽  
Author(s):  
A. M. Benjamin ◽  
J. H. Quastel

High concentrations (105 μequiv./ml) of potassium ions in the incubation medium bring about reduced uptakes of L-glutamate, L-aspartate, and glycine but not of L-glutamine into rat brain cortex slices incubated aerobically in a physiological saline – glucose medium. The reductions are suppressed by acetylcholine (20 μM – 2 mM) in presence of eserine (0.1 mM) and not by tetrodotoxin (3 μM). The effect of acetylcholine is calcium dependent. It is diminished by atropine but not by d-tubocurarine (1 mM). Protoveratrine (5 μM) inhibition of amino acid uptake is not affected by acetylcholine but it is suppressed by tetrodotoxin. Acetylcholine and tetrodotoxin act independently of each other. Acetylcholine suppresses the potassium-evoked release of endogenous glutamate, aspartate, or glycine from incubated rat brain cortex slices. Its action on release is calcium dependent. Acetylcholine also suppresses the potassium-induced release of amino acids from rat brain cortex slices that have been previously incubated with 2 mM sodium L-glutamate or 2 mM sodium L-aspartate.It is suggested that increased cell concentrations of calcium ions, owing to high concentrations of potassium ions in the incubation medium, cause an increased glial permeability to sodium ions, with a resultant diminution of the sodium gradient. This diminution is considered to be responsible for the diminished concentrative uptake of L-glutamate, L-aspartate, or glycine, and the increased release of these amino acids. Acetylcholine suppresses the permeability change due to high concentrations of potassium ions and reverses the changed sodium gradient and the consequent change in amino acid uptake and release. It would seem that accumulation of acetylcholine in the intracellular spaces may affect glia, as well as neurons, modifying permeability to sodium ions and to various amino acids now assuming importance as possible transmitters.


1962 ◽  
Vol 40 (1) ◽  
pp. 1591-1602 ◽  
Author(s):  
P. N. Abadom ◽  
P. G. Scholefield

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.


1968 ◽  
Vol 46 (6) ◽  
pp. 543-548 ◽  
Author(s):  
S. Nakazawa ◽  
J. H. Quastel

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.


1961 ◽  
Vol 39 (12) ◽  
pp. 1811-1827 ◽  
Author(s):  
A. Vardanis ◽  
J. H. Quastel

The effects of tetraethyl lead, tetraethyl tin, triethyl lead, and triethyl tin on the metabolism of rat brain cortex slices have been studied. Tetraethyl lead and tetraethyl tin inhibit the active transport of amino acids into rat brain cortex slices at concentrations and under conditions that show no effect on the glucose metabolism of the slices. Tetraethyl lead and tetraethyl tin inhibit the oxidation of L-glutamate by rat brain slices. This effect can be accounted for on the basis of the inhibitory action of these two substances on the transport of the amino acid into the brain tissue.Tetraethyl lead and tetraethyl tin abolish, at low concentrations, potassium-stimulated brain slice respiration in presence of glucose, having little or no effect on unstimulated brain slice respiration. However, the respiration of rat brain cortex slices previously treated with phospholipase A is highly sensitive to tetraethyl lead.The inhibitory effects of the two tetraethyl compounds show differences from those of their triethyl derivatives indicating that the effects of the former substances are not due to admixture with, or conversion to, the latter substances.The brain slices of rats poisoned with either tetraethyl lead or tetraethyl tin are unable to effect the active transport of amino acids. The appearance of this biochemical abnormality coincides with the manifestation of neuropathological symptoms.The mode of action of tetraethyl lead and of tetraethyl tin on brain metabolism in vitro is discussed. It is suggested that they may act on phospholipid groups concerned with amino acid and cation transport at the cell membrane.


1968 ◽  
Vol 46 (4) ◽  
pp. 363-365 ◽  
Author(s):  
S. Nakazawa ◽  
J. H. Quastel

Acetylcholine reverses the inhibitory action of a high potassium ion concentration on glycine uptake into rat brain cortex slices incubated in a physiological Ringer–glucose medium. The effect of acetylcholine, which may take place at 0.02 mM, is enhanced by the presence of eserine which itself is without effect. Choline and hemicholinium at equivalent concentrations are also without effect. The reversing action of acetylcholine is specific, as it cannot reverse the inhibitory action of ammonium ions, ouabain, L-glutamate, or L-glutamine on glycine transport into the brain. As the presence of acetylcholine does not affect the ATP level, it is suggested that it acts by promoting the influx of sodium ions, which have a controlling effect on the amino acid influx.


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