Effects of acetylcholine on potassium-induced changes of some amino acid uptakes and release in cerebral cortex slices from the rat

1977 ◽  
Vol 55 (3) ◽  
pp. 347-355 ◽  
Author(s):  
A. M. Benjamin ◽  
J. H. Quastel
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Rat Brain ◽  
Brain Cortex ◽  
Potassium Ions ◽  
Acid Uptake ◽  
Rat Brain Cortex ◽  
Brain Cortex Slices ◽  
High Concentrations ◽  
Cortex Slices

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.

THE EFFECTS OF LEAD AND TIN ORGANOMETALLIC COMPOUNDS ON THE METABOLISM OF RAT BRAIN CORTEX SLICES

1961 ◽  
Vol 39 (12) ◽  
pp. 1811-1827 ◽  
Author(s):  
A. Vardanis ◽  
J. H. Quastel
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Rat Brain ◽  
Brain Slice ◽  
Brain Cortex ◽  
Brain Slices ◽  
Tetraethyl Lead ◽  
Rat Brain Cortex ◽  
Brain Cortex Slices ◽  
Cortex Slices

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.

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.

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.

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.

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 (12) ◽  
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.

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