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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 277 (1973), S. 323-332 
    ISSN: 1432-1912
    Keywords: Chloral Hydrate ; Trichloroethanol ; Isolated Perfused Rat Brain ; High-Energy Phosphates ; Glycolytic Pathway
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The isolated perfused rat brain was used for a comparative study of the effects of chloral hydrate and trichloroethanol on cerebral energy metabolism. After a perfusion period of 30 min the brain levels of the following substrates and metabolites were measured spectrophotometrically: P-creatine, creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6-P, fructose diphosphate, α-glycero-P, dihydroxyacetone-P, pyruvate, lactate, glutamate, α-ketoglutarate and ammonia. Furthermore, the concentration of chloral hydrate and trichloroethanol in the isolated brain and in the perfusion medium was measured colorimetrically. Little more than 10% of chloral hydrate in the isolated brain and in the perfusion medium were reduced to trichloroethanol. In intact animals there were about 70% of chloral hydrate transformed. Chloral hydrate and trichloroethanol caused an accumulation of P-creatine, no change in the lactate/pyruvate ratio, an increase of the glucose concentration and a decrease of glucose-6-P level in the isolated brain. The rise of brain glucose level was more pronounced after trichloroethanol than after chloral hydrate. The effects of chloral hydrate and trichloroethanol on brain glucose and glucose-6-P levels suggest an inhibition of brain hexokinase activity by these drugs.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 275 (1972), S. 124-134 
    ISSN: 1432-1912
    Keywords: Isolated Perfused Rat Brain ; High-Energy Phosphates ; Glycolytic Pathway ; Phenobarbital ; Ischemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The concentrations of P-creatine, creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6-P, fructose diphosphate, dihydroxyacetone-P, α-glycero-P, lactate and pyruvate were measured in the isolated perfused rat brain as well as in rat brain in vivo. Similar levels were observed in the isolated brain and in intact animals, and the values measured were in good accordance with those described in the literature. Only the pyruvate and lactate content were significantly higher in the isolated brain but the lactate/pyruvate ratio remained unchanged. An anesthetic or ischemia caused just the same effects on energy metabolism of the isolated rat brain as described for intact animals. Thus, 1.5 mM phenobarbital in the perfusion medium produced a statistically significant increase in P-creatine and glucose levels as well as a decrease of pyruvate, lactate and α-glycero-P levels. After ischemia of the isolated brain the concentrations of high-energy phosphates, glycogen, glucose, and pyruvate fell considerably concomitantly with significant accumulations of creatine, AMP, α-glycero-P and lactate. The results indicate that the isolated perfused rat brain may be a useful tool for studying cerebral metabolism.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 289 (1975), S. 399-407 
    ISSN: 1432-1912
    Keywords: Isolated Perfused Rat Brain ; High-Energy Phosphates ; Glycolytic Pathway ; Thiopental
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of glucose concentrations in the perfusion medium ranging from 5 to 15 mM and thiopental, on cerebral energy metabolism were studied using the isolated perfused rat brain. After a perfusion time of 30 min brain levels of the following substrates and metabolites were determined: P-creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6-P, fructose-6-P, pyruvate, lactate, α-ketoglytarate, glutamate, ammonia. In control experiments increasing the glucose concentration in the perfusion medium produced an increase of intracellular brain glucose concentration only, revealing a linear relationship between glucose content in brain and blood. Neither high-energy phosphates nor glycolytic intermediates were markedly affected by the changes in blood glucose. With an anesthetic dose of thiopental (0.15 mM) in the perfusion medium identical metabolic alterations occurred in all experiments: P-creatine and glucose were significantly increased whereas ADP, AMP, lactate and pyruvate were diminished. Also with thiopental brain glucose was linearly related with the glucose concentration in the perfusion medium. The calculated regression line was apparently parallel with that from control experiments; that means thiopental always caused an elevation of brain glucose by the same amount of 0.9 μmoles/g—irrespective of the initial cerebral glucose content. The results yield further evidence that glucose transport is not the rate-limiting step in glycolysis. The action of thiopental on glycolytic pathway is discussed.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 279 (1973), S. 243-254 
    ISSN: 1432-1912
    Keywords: Neuroleptics ; Antidepressants ; Isolated Perfused Rat Brain ; High Energy Phosphates ; Glycolytic Pathway
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The isolated perfused rat brain was used for a comparative study of the effects of promazine, imipramine, monodesmethyl promazine and desipramine on cerebral energy metabolism. After perfusion for 30 min or 1 h the brain levels of the following substrates and metabolites were estimated: P-creatine, creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6-P, fructose diphosphate, dihydroxyacetone-P, pyruvate, lactate, α-ketoglutarate, and ammonia. Drug concentrations of 5·10−6 M and 10−5 M in the perfusion medium caused a significant decrease of glucose-6-P alone. When the drug concentration was raised to a toxic range (10−4 M), reflected in the EEG by the pattern of secondary discharges, an accumulation of P-creatine and glucose and a decrease of glycogen, glucose-6-P and ammonia occurred; the lactate/pyruvate ratios remained unchanged. As there were no qualitative differences between the effects of the investigated neuroleptics and antidepressants on cerebral metabolism, these effects might be unspecific and not correlated with the pharmacological action of the drugs.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 290 (1975), S. 323-327 
    ISSN: 1432-1912
    Keywords: 6-Aminonicotinamide ; Glycolytic Pathway ; Isolated Perfused Rat Brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cerebral energy metabolism was studied in the isolated perfused rat brain after 6-aminonicotinamide (6-AN; 35 mg/kg i.p.) administered to the intact animals 7 hrs before perfusion was started. The metabolic alterations in the isolated rat brains were such as reported for rat and mouse brain in vivo: Inhibition of 6-phosphogluconate dehydrogenase was followed by an accumulation of 6-phosphogluconate, leading to a decreased activity of glucosephosphate isomerase. This was reflected by increased levels of glucose and glucose 6-phosphate and decreased levels of fructose 6-phosphate, pyruvate and lactate. Since the concentration of lactate in the perfusate of the isolated brain was also lowered, 6-AN must have reduced the glycolytic flux rate.
    Type of Medium: Electronic Resource
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