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.

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.

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.

STUDIES OF THE CATIONIC, AND ACETYLCHOLINE, STIMULATION OF PHOSPHATE INCORPORATION INTO PHOSPHOLIPIDS IN RAT BRAIN CORTEX IN VITRO

1963 ◽  
Vol 41 (5) ◽  
pp. 1243-1256 ◽  
Author(s):  
Maurice Brossard ◽  
J. H. Quastel
Keyword(s):  
Rat Brain ◽  
Brain Cortex ◽  
Total Phospholipid ◽  
Sodium Ions ◽  
Inorganic P ◽  
Rat Brain Cortex ◽  
Brain Cortex Slices ◽  
Cortex Slices ◽  
Stimulation Of

The addition of 0.1 M KCl to, or the omission of CaCl2from, incubation media in which rat brain cortex slices are respiring, stimulates the incorporation of inorganic P32into phospholipids. It also stimulates the labelling of 7-minute hydrolyzable nucleotide phosphates, but decreases their levels. The stimulation of P32incorporation into total phospholipid takes place primarily into phosphatidic acid and phosphoinositide but not into phosphatidyl choline and phosphatidyl ethanolamine. The addition of succinate and γ-aminobutyrate to brain cortex slices, metabolizing glucose, markedly inhibits the labelling of phospholipids although the respiration of slices is not diminished. The potassium stimulation of phospholipid labelling only occurs if sodium ions are present in the incubation medium. The lesser stimulation due to absence of calcium ions seems, however, to be independent of the presence of sodium ions. Acetylcholine stimulation of P32incorporation into phospholipids is dependent on the presence of sodium ions. Such stimulations are suppressed by concentrations of malonate, iodoacetate, fluoride, and ethanol that have little effect on the unstimulated incorporation of P32. Atropine and hyoscine inhibit acetylcholine stimulation but not cationic stimulation of P32incorporation. It is suggested that the effect of acetylcholine on P32incorporation is mediated by cationic changes at the nerve cell membrane.

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.

STUDIES OF THE CATIONIC, AND ACETYLCHOLINE, STIMULATION OF PHOSPHATE INCORPORATION INTO PHOSPHOLIPIDS IN RAT BRAIN CORTEX IN VITRO

1963 ◽  
Vol 41 (1) ◽  
pp. 1243-1256 ◽  
Author(s):  
Maurice Brossard ◽  
J. H. Quastel
Keyword(s):  
Rat Brain ◽  
Brain Cortex ◽  
Total Phospholipid ◽  
Sodium Ions ◽  
Inorganic P ◽  
Rat Brain Cortex ◽  
Brain Cortex Slices ◽  
Cortex Slices ◽  
Stimulation Of

The addition of 0.1 M KCl to, or the omission of CaCl2from, incubation media in which rat brain cortex slices are respiring, stimulates the incorporation of inorganic P32into phospholipids. It also stimulates the labelling of 7-minute hydrolyzable nucleotide phosphates, but decreases their levels. The stimulation of P32incorporation into total phospholipid takes place primarily into phosphatidic acid and phosphoinositide but not into phosphatidyl choline and phosphatidyl ethanolamine. The addition of succinate and γ-aminobutyrate to brain cortex slices, metabolizing glucose, markedly inhibits the labelling of phospholipids although the respiration of slices is not diminished. The potassium stimulation of phospholipid labelling only occurs if sodium ions are present in the incubation medium. The lesser stimulation due to absence of calcium ions seems, however, to be independent of the presence of sodium ions. Acetylcholine stimulation of P32incorporation into phospholipids is dependent on the presence of sodium ions. Such stimulations are suppressed by concentrations of malonate, iodoacetate, fluoride, and ethanol that have little effect on the unstimulated incorporation of P32. Atropine and hyoscine inhibit acetylcholine stimulation but not cationic stimulation of P32incorporation. It is suggested that the effect of acetylcholine on P32incorporation is mediated by cationic changes at the nerve 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.

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