scholarly journals Acetoacetate metabolism in infant and adult rat brain in vitro

1970 ◽  
Vol 116 (4) ◽  
pp. 641-655 ◽  
Author(s):  
T. Itoh ◽  
J. H. Quastel
Keyword(s):  
Rat Brain ◽  
Brain Cortex ◽  
Brain Slices ◽  
Adult Brain ◽  
Adult Rat ◽  
Infant Rat ◽  
Rat Brain Cortex ◽  
Adult Rat Brain ◽  
Brain Cortex Slices ◽  
Cortex Slices

1. Acetoacetate or dl-β-hydroxybutyrate increases the rate of oxygen consumption to a smaller extent than that brought about by glucose or pyruvate in adult rat brain-cortex slices but to the same extent as that in infant rat brain-cortex slices. 2. The rate of 14CO2 evolution from [1-14C]glucose considerably exceeds that from [6-14C]glucose in respiring infant rat brain-cortex slices, in contrast with adult brain-cortex slices, suggesting that the hexose monophosphate shunt operates at a greater rate in the infant rat brain than in the adult rat brain. 3. The rate of 14CO2 evolution from [3-14C]acetoacetate or dl-β-hydroxy[3-14C]butyrate, in the absence of glucose, is the same in infant rat brain slices as in adult rat brain slices. It exceeds that from [2-14C]glucose in infant rat brain but is less than that from [2-14C]glucose in adult rat brain. 4. Acetoacetate is oxidized in the brain through the operation of the citric acid cycle, as shown by the accelerating effect of glucose on acetoacetate oxidation in adult brain slices, by the inhibitory effects of malonate in both infant and adult brain slices and by its conversion into glutamate and related amino acids in both tissues. 5. Acetoacetate does not affect glucose utilization in adult or infant brain slices. It inhibits the rate of 14CO2 formation from [2-14C]glucose or [U-14C]-glucose the effect not being wholly due to isotopic dilution. 6. Acetoacetate inhibits non-competitively the oxidation of [1-14C]pyruvate, the effect being attributed to competition between acetyl-CoA and CoA for the pyruvate-oxidation system. 7. Acetoacetate increases the rate of aerobic formation of lactate from glucose with both adult and infant rat brain slices. 8. The presence of 0.1mm-2,4-dinitrophenol diminishes but does not abolish the rate of 14CO2 formation from [3-14C]acetoacetate in rat brain slices. This points to the participation of ATP in the process of oxidation of acetoacetate in infant or adult rat brain. 9. The presence of 5mm-d-glutamate inhibits the rate of 14CO2 formation from [3-14C]acetoacetate, in the presence or absence of glucose. 10. Labelled amino acids are formed from [3-14C]acetoacetate in both adult and infant rat brain-cortex slices, but the amounts are smaller than those found with [2-14C]glucose in adult rat brain and greater than those found with [2-14C]glucose in infant rat brain. 11. Acetoacetate is not as effective as glucose as a precursor of acetylcholine in adult rat brain but is as effective as glucose in infant rat brain slices. 12. Acetoacetate or β-hydroxybutyrate is a more potent source of acetyl-CoA than is glucose in infant rat brain slices but is less so in adult rat brain slices.

Inhibition of Rat Brain Protein and Nucleic Acid Synthesis by Cannabinoids In Vitro

1972 ◽  
Vol 50 (6) ◽  
pp. 654-662 ◽  
Author(s):  
Alexander Jakubovič ◽  
Patrick L. McGeer
Keyword(s):  
Nucleic Acid ◽  
Rat Brain ◽  
Brain Cortex ◽  
Weight Fraction ◽  
Adult Rat ◽  
Rat Brain Cortex ◽  
Adult Rat Brain ◽  
Brain Cortex Slices ◽  
Cortex Slices

The effect of Δ9-tetrahydrocannabinol (THC), cannabidiol, and cannabigerol on some metabolic processes in infant and adult rat brain cortex slices was studied in vitro. With L-leucine-U-14C as the tracer substrate, the incorporation of radioactivity into the protein and nucleic acid fractions was significantly inhibited by THC. The oxygen consumption of the slices, the uptake of L-leucine into the slices, and the evolution of 14CO2 were, however, unaffected by THC. Cannabidiol was comparable in activity to THC but cannabigerol was less active. The pattern of inhibition by THC was also observed when the rat brain cortex slices were stimulated by 100 mM K+ or 10 μM protoveratrine. THC also brought about a significant decrease in the incorporation of uridine-2-14C into the nucleic acid fraction of infant and adult rat brain cortex slices. There was a decreased formation of uridine nucleotides in the presence of THC and an increase in uridine and uracil in the low molecular weight fraction. Experiments with THC-2,4-14C established that there was rapid uptake and a concentration of radioactivity in the incubated brain tissue.

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.

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.

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