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 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.

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.

UPTAKE OF 5-HYDROXYTRYPTOPHAN-3-C14 AND ITS METABOLISM IN RAT BRAIN CORTEX SLICES

1962 ◽  
Vol 40 (1) ◽  
pp. 1439-1448
Author(s):  
J. P. von Wartburg
Keyword(s):  
Monoamine Oxidase ◽  
Synergistic Effect ◽  
Rat Brain ◽  
Brain Cortex ◽  
Brain Slices ◽  
Inhibitory Effect ◽  
Rat Brain Cortex ◽  
Brain Cortex Slices ◽  
Cortex Slices

Rat brain cortex slices were incubated with 5-hydroxytryptophan-3-C14. A method for determination of 5-hydroxytryptamine-C14 and 5-hydroxyindolacetic acid-C14 formed in brain slices is described. Effects of inhibitors of 5-hydroxytryptophan decarboxylase and monoamine oxidase on the metabolic pathway of 5-hydroxytryptophan-3-C14 were measured. α-Methyl dopa (0.33 mM) decreased the level of 5-hydroxyindolacetic acid to a greater amount than that of 5-hydroxytryptamine. Iproniazid (3.3 mM) resulted in an accumulation of 5-hydroxytryptamine and a decrease of 5-hydroxyindolacetic acid formation of 65%. Pheniprazine (0.1 mM) exerted an inhibitory effect on both 5-hydroxytryptophan decarboxylase and monoamine oxidase. Chlorpromazine (0.5 mM) decreased the level of 5-hydroxytryptamine 60% and had a synergistic effect with the inhibition on respiration of brain slices and 5-hydroxytryptophan transport exerted by 0.2 M n-propanol.

UPTAKE OF 5-HYDROXYTRYPTOPHAN-3-C14 AND ITS METABOLISM IN RAT BRAIN CORTEX SLICES

1962 ◽  
Vol 40 (10) ◽  
pp. 1439-1448 ◽  
Author(s):  
J. P. von Wartburg
Keyword(s):  
Monoamine Oxidase ◽  
Synergistic Effect ◽  
Rat Brain ◽  
Brain Cortex ◽  
Brain Slices ◽  
Inhibitory Effect ◽  
Rat Brain Cortex ◽  
Brain Cortex Slices ◽  
Cortex Slices

Rat brain cortex slices were incubated with 5-hydroxytryptophan-3-C14. A method for determination of 5-hydroxytryptamine-C14 and 5-hydroxyindolacetic acid-C14 formed in brain slices is described. Effects of inhibitors of 5-hydroxytryptophan decarboxylase and monoamine oxidase on the metabolic pathway of 5-hydroxytryptophan-3-C14 were measured. α-Methyl dopa (0.33 mM) decreased the level of 5-hydroxyindolacetic acid to a greater amount than that of 5-hydroxytryptamine. Iproniazid (3.3 mM) resulted in an accumulation of 5-hydroxytryptamine and a decrease of 5-hydroxyindolacetic acid formation of 65%. Pheniprazine (0.1 mM) exerted an inhibitory effect on both 5-hydroxytryptophan decarboxylase and monoamine oxidase. Chlorpromazine (0.5 mM) decreased the level of 5-hydroxytryptamine 60% and had a synergistic effect with the inhibition on respiration of brain slices and 5-hydroxytryptophan transport exerted by 0.2 M n-propanol.

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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