The Effects of Lead and Tin Organometallic Compounds on the Metabolism of Rat Brain Cortex Slices

Vardanis, A.; Quastel, J. H.

doi:10.1139/o61-202

Cited by 33 publications

(13 citation statements)

References 7 publications

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“…It is generally accepted that the cell membrane, or more specifically its phospholipid layer, is the surface structure that is principally responsible not only for preventing effiux of various small molecules concentrated within cells (12) but also for transport of various amino acids (10,20). Our previous papers reported that both ctotrimazole and miconazole have a preferential affinity at Universitaetsbibliothek Giessen on May 15, 2015 http://sabouraudia.oxfordjournals.org/ from for certain membrane phospholipids of sensitive fungi (9,23,24).…”

Section: Discussionmentioning

confidence: 99%

Effect of two imidazole antimycotics, clotrimazole and miconazole on amino acid transport inCandida albicans

Yamaguchi

Iwata

1979

Med Mycol

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Effect of the two imidazole antimycotics, clotrimazole and miconazole, on the uptake of leucine, lysine and several other amino acids by starved cells of Candida albicans was studied. Both imidazoles at concentrations around the minimum growth-inhibitory concentration substantially decreased the rate of uptake and the level in the pool of these amino acids when the cells were incubated in the absence of glucose. Inhibition by the 2 imidazoles, particularly clotrimazole, of uptake of leucine or lysine was markedly antagonized by exogenous glucose. However, such a protective effect of glucose was completely nullified when blasticidin S, a preferential inhibitor of protein synthesis, was added to the cells along with glucose. Under all of these experimental conditions, the 2 imidazoles inhibited the accumulation of leucine in the intracellular pool more profoundly than the corresponding overall incorporation of this amino acid into proteins.-The imidazoles caused an efflux of previously accumulated leucine at drug concentrations comparable to those producing appreciable inhibitioa of_leucine uptake. On ~he basis-of its antifup~gal activity, miconazole appeared to be more potent in this membrane action than clotrimazole, particularly in the presence of exogenous glucose, although there was no qualitative difference between the mcchanism of action of the two imidazoles.The initial reports (5, 13) on the potent antifungai activity of two new imidazole derivatives, clotrimazole (1-[O-chloro-0¢,c~-diphenylbenzyl] imidazole) and miconazole (1-[2,4, dichloro-fl-(2-4-dichlorobenzyloxy)-phenyl] imidazole nitrate), have prompted further laboratory and clinical studies of these and related imidazole antimycotics. Although the exact mechanisms of antifungal activity of-imidazoles remain to be elucidated, a limited number of papers have suggested that the primary site of action of both clotrimazole and miconazole is on the cell membrane of sensitive organisms (7,8,9,15,23). It appears that both imidazoles disturb the permeability characteristics of the membrane and allow leakage of essential precursors, metabolites, ions and other intracellular componenM, with consequent inhibition of macromolecular synthesis. However, it is also conceivable that imidazole inhibition of macromolecular synthesis may reflect, at least partly, an alteration in the membrane function responsible for the cellular uptake of some essential precursors from the growth environment.In this paper we have examined the effect of clotrimazole and miconazole on transmembrane transport of several amino acids in Candida albicans grown under different experimental conditions. MATERIALS AND METHODSOrganism and culture conditions C. albicans MTU 12021 was maintained on Sabouraud dextrose agar slopes at 25 °C and subcultured every month. Fungi removed from the slopes with sterile saline were inoculated into 100 ml PY medium, which consisted of 1%0 Bactopeptone (Difco) and 0"5 % yeast extract (Difco), and cultures were grown at 37 °C for 24h 3llat Universitaetsbiblioth...

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Section: Discussionmentioning

confidence: 99%

Effect of two imidazole antimycotics, clotrimazole and miconazole on amino acid transport inCandida albicans

Yamaguchi

Iwata

1979

Med Mycol

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“…However, the extent of amino acid transport into brain cortex slices is proportional to the level of ATP in the slices, and aIanine and phenylalanine have little effect on glycine transport in nerve cells (5). The mechanism of amino acid uptake by brain mitochondria is therefore deemed to be a different process from the transport of amino acids a t the brain cell membrane (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), and also a different process from the accumulation of noradrenaline by brain mitochondrial particles (221, which is inhibited by mo~aovalent cations such as sodium.…”

Section: Discussionmentioning

confidence: 99%

The Uptake of Glycine by Rat Brain Mitochondria

Nukada¹

1965

Can. J. Biochem.

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Rat brain mitochondria1 pellets are able to accumulate glycine by a sodiumdependent and ouabain-sensitive process which is not potassium dependent. This process does not occur in liver or kidney mitochondria. Glycine uptake by brain mitochondria is not affected by the addition of ATP, NAB, or other cofactors, but it is inhibited by dinitrophenol and, competitively, by certain amino acids. Data obtained by the use of various concentrations of sodium ions or of sucrose indicate that the uptake of glycine by brain mitochondria is closely linked with their structural integrity.

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“…This solution was given to 5-week-old male rats intraperitoneally at a dosage of 15 mg/kg body weight once daily. At this concentration, the animals developed convulsions after five or six doses (Vardanis and Quastel, 1961). For control, the same concentration of n-propanol alone was given.…”

Section: Methodsmentioning

confidence: 99%

“…Patel et al (1974) suggested that the decreased labelling of amino acids from glucose in inorganic lead toxicity could be due to depression of glucose utilisation. Glucose uptake by brain was not inhibited, and therefore the decreased glucose utilisation was not due to decreased availability of glucose (Cremer, 1959;Vardanis and Quastel, 1961;Patel et al, 1974). The inhibition of lipoyl dehydrogenase, a component of the pyruvate dehydrogenase (PDH) and aketoglutarate dehydrogenase complexes, by lead has been reported (Ulmer and Vallee, 1969).…”

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Pyruvate Metabolism in the Brain of Young Rats Intoxicated with Organic and Inorganic Lead

Regunathan

Sundaresan

1984

Journal of Neurochemistry

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The activities of lipoyl dehydrogenase, aspartate transaminase, and alanine transaminase, and levels of lactate were estimated in cerebral cortex, cerebellum, and brainstem of rats intoxicated acutely with tetraethyl lead and chronically with lead acetate. A significant inhibition of lipoyl dehydrogenase was observed in both groups of animals, whereas transaminase activities were increased in inorganic lead toxicity. Oxidative decarboxylation and anaplerosis of pyruvate was assessed in brain slices using [1-14C]pyruvate. Pyruvate dehydrogenase activity was decreased in both organic and inorganic lead toxicity, whereas labelling of aspartate and alanine was increased in inorganic lead toxicity. In studies in vitro, lead acetate showed a more significant effect than tetraethyl lead. The higher anaerobic metabolism in inorganic lead toxicity, as evidenced by increased anaerobic lactate production by brain slices, could either be an adaptive mechanism or be due to the delayed maturation of brain in the developing rat. Such a mechanism does not occur in acute organic lead toxicity, as the compound brings about massive and rapid degenerative changes in brain, resulting in convulsive seizures and death of the animals.

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The Effects of Lead and Tin Organometallic Compounds on the Metabolism of Rat Brain Cortex Slices

Cited by 33 publications

References 7 publications

Effect of two imidazole antimycotics, clotrimazole and miconazole on amino acid transport inCandida albicans

Effect of two imidazole antimycotics, clotrimazole and miconazole on amino acid transport inCandida albicans

The Uptake of Glycine by Rat Brain Mitochondria

Pyruvate Metabolism in the Brain of Young Rats Intoxicated with Organic and Inorganic Lead

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