Effects of pentylenetetrazole and glutamate on metabolism of [U-13C]glucose in cultured cerebellar granule neurons

Eloqayli, Haytham; Qu, Hong; Unsgård, Geirmund; Sletvold, Olav; Hadidi, H.; Sonnewald, Ursula

doi:10.1016/s0197-0186(01)00073-0

Cited by 14 publications

(15 citation statements)

References 37 publications

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“…This is in partial agreement with the results from Eloqayli and co-workers who demonstrated decreased mitochondrial metabolism and glycolysis in astrocytes acutely exposed to PTZ in vitro (Eloqayli et al 2002) and also with the findings of Bruno et al (2002) who demonstrated increased hydrolysis of nucleosides in blood serum from acute PTZ-treated rats.…”

Section: Discussionsupporting

confidence: 92%

Influence of Midazolam and L-Arginine on Clinical Observations and Biochemical Changes in Rat Liver Induced by Pentylenetetrazole

et al. 2009

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Certain types of convulsions may lead to multiorgan dysfunction. We investigated whether the chemoconvulsant pentylenetetrazole (PTZ) could influence energy synthesis in the liver besides evoking convulsions in adult male Wistar rats. In 80% of the rats PTZ (100 mg/kg body weight, administered intraperitoneally -i.p.) evoked generalised clonic convulsions (GCCs) and in 60% of the rats generalised clonic-tonic convulsions (GCTCs) within 4 min after its administration. Cytochrome c oxidase activity was simultaneously reduced approximately three-fold compared to 0.9% NaCl-treated (control) rats (p < 0.01). Midazolam administered before PTZ was an excellent anti-convulsant especially against GCCs (p < 0.05). However, it did not protect against the decrease in cytochrome c oxidase activity induced by PTZ. In contrast to midazolam, pretreatment with L-arginine did not prevent PTZ-evoked convulsions. However, it offered some protection against the PTZ-mediated reduction in cytochrome c oxidase activity. Our results open new avenues of research that will focus on the mechanisms of action of PTZ, midazolam and L-arginine with particular reference to their direct and/or indirect effects on liver function. Convulsions, cytochrome c oxidase, liver, midazolam, pentylenetetrazoleDespite years of studies the pathophysiological mechanisms underlying epilepsy are still not completely understood. In particular multiple questions remain to be answered, mainly relating to epileptic therapy which still faces a high failure rate. Several general anaesthetics and benzodiazepines that are regularly used in surgical practice are often administered for the treatment of epileptic seizures (Rossetti 2007;Holtkamp 2007;Riss et al. 2008). However, there are little published data concerning biochemical changes in organs apart from the brain, particularly during and after epileptic seizures (Akbas et al. 2005). In our current study emphasis was placed on determining changes in energy synthesis in the liver during convulsions and defining the effect of midazolam, a benzodiazepine commonly used in human and veterinary surgery, as well as the effect of L-arginine.Mitochondria are organelles whose main role is energy production. Accordingly, they are key components for determining cell survival. In contrast to smooth external membrane the inner mitochondrial membrane is wrinkled and forming crypts (cristae). As the number of crypts is directly proportional to the cell's energy demands, cells within the regions of the brain and liver tissue have the highest number of crypts.Important oxido-reductive processes occur in mitochondria which result in the synthesis of adenosine triphosphate (ATP). The latter is an energy-rich compound responsible for the vast majority of processes requiring a high energy transfer (Kakkar and Singh 2007).Reducing equivalents, such as NADH, are formed in the cytoplasm during glycolysis and are transported into mitochondria in order to assist the process of oxidative phosphorylation. The transfer of electrons from ...

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Section: Discussionsupporting

confidence: 92%

Influence of Midazolam and L-Arginine on Clinical Observations and Biochemical Changes in Rat Liver Induced by Pentylenetetrazole

et al. 2009

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“…Tricarboxylic acid cycling may in any given microenvironment be monitored using labeling of glutamate since aspartate aminotransferase activity is several fold higher than that of the TCA cycling (Drejer et al, 1985;Fitzpatrick et al, 1990;Mason et al, 1992). The enzymatic pathways involved in the conversion of glucose/lactate to glutamate including glycolysis, lactate dehydrogenase, and TCA cycle reactions are most likely compartmentalized and heterogeneous (Eloqayli et al, 2002;Waagepetersen et al, 2003, and references therein). However, the MCL of glutamate is an average value of the labeling generated in all compartments metabolizing the labeled substrate and it is at present not possible to analyze this parameter completely with regard to complexity.…”

Section: Resultsmentioning

confidence: 99%

Glucose is Necessary to Maintain Neurotransmitter Homeostasis during Synaptic Activity in Cultured Glutamatergic Neurons

Bak¹,

Schousboe²,

Sonnewald

et al. 2006

J Cereb Blood Flow Metab

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154

168

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Glucose is the primary energy substrate for the adult mammalian brain. However, lactate produced within the brain might be able to serve this purpose in neurons. In the present study, the relative significance of glucose and lactate as substrates to maintain neurotransmitter homeostasis was investigated. Cultured cerebellar (primarily glutamatergic) neurons were superfused in medium containing [U-13 C]glucose (2.5 mmol/L) and lactate (1 or 5 mmol/L) or glucose (2.5 mmol/L) and [U-13 C]lactate (1 mmol/L), and exposed to pulses of N-methyl-D-aspartate (300 lmol/L), leading to synaptic activity including vesicular release. The incorporation of 13 C label into intracellular lactate, alanine, succinate, glutamate, and aspartate was determined by mass spectrometry. The metabolism of [U-13 C]lactate under non-depolarizing conditions was high compared with that of [U-13 C]glucose; however, it decreased significantly during induced depolarization. In contrast, at both concentrations of extracellular lactate, the metabolism of [U-13 C]glucose was increased during neuronal depolarization. The role of glucose and lactate as energy substrates during vesicular release as well as transporter-mediated influx and efflux of glutamate was examined using preloaded D-[ 3 H]aspartate as a glutamate tracer and DL-threo-b-benzyloxyaspartate to inhibit glutamate transporters. The results suggest that glucose is essential to prevent depolarization-induced reversal of the transporter (efflux), whereas vesicular release was unaffected by the choice of substrate. In conclusion, the present study shows that glucose is a necessary substrate to maintain neurotransmitter homeostasis during synaptic activity and that synaptic activity does not induce an upregulation of lactate metabolism in glutamatergic neurons.

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“…Assignments were made by comparison with chemical shifts reported in the literature (Cerdan et al, 1990;Eloqayli et al, 2002;Fan, 1996).…”

Section: C Nmr Spectroscopy Analysismentioning

confidence: 99%

Improving retroviral vectors production: Role of carbon sources in lipid biosynthesis

Amaral

Coroadinha

Merten

et al. 2008

Journal of Biotechnology

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Effects of pentylenetetrazole and glutamate on metabolism of [U-13C]glucose in cultured cerebellar granule neurons

Cited by 14 publications

References 37 publications

Influence of Midazolam and L-Arginine on Clinical Observations and Biochemical Changes in Rat Liver Induced by Pentylenetetrazole

Influence of Midazolam and L-Arginine on Clinical Observations and Biochemical Changes in Rat Liver Induced by Pentylenetetrazole

Glucose is Necessary to Maintain Neurotransmitter Homeostasis during Synaptic Activity in Cultured Glutamatergic Neurons

Improving retroviral vectors production: Role of carbon sources in lipid biosynthesis

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