Brain cortical amino acids measured by intracerebral dialysis in portacaval shunted rats

Abstract

The extracellular amino acid content was measured in the parietal cortex in portacaval and sham operated rats, using the brain dialysis technique. The amino acid content of the perfusate was determined for 10 min before and during stimulation with potassium chloride. Basal levels of aspartate, glutamine, glycine, methionie, valine, phenylalanine and leucine were 2-to 6-fold higher in the PC-shunted as compared to the sham operated rats. For glutamate, taurine, and GABA no differences were observed between the two groups. After KCl stimulation the release of glutamate and GABA increased significantly in both groups. For GABA this rise was approximately twice as high in the PC-shunted rats (+300%, P less than 0.01) as in the sham operated rats (+150%, P less than 0.01 as compared to basal). In the sham operated, but not in the PC-shunted rats, methionine and valine levels rose significantly (+200%, P less than 0.05) and glutamine release decreased (-50%, P less than 0.05). These findings suggest that the brain metabolism of amino acids is altered after a portacaval shunt. This could in turn alter the neurotransmission and partly explain the low spontaneous motor activity seen in these animals.

Portal-Systemic Encephalopathy: A Disorder of Neuron-Astrocytic Metabolic Trafficking

“…This evidence can be summarized as follows: (1) As already stated in this arti cle, exposure o f cultured astrocytes to concentrations of ammonia equivalent to those reported in brain in experi mental PSE results in decreased capacity for glutamate uptake [28]; (2) blood extracts from patients with PSE inhibit the high affinity glutamate uptake system in rat hippocampal slices [35]; (3) high-affinity uptake of gluta mate into rat brain synaptosomes is significantly de creased by exposure to 5 mM ammonia [36]; (4) electri cally stimulated, Ca2 f-dependent (i.e., neuronal) release of glutamate from hippocampal slices from portacaval shunted rats is significantly increased [37], consistent with decreased reuptake into the presynaptic terminal and perineuronal astrocyte; (5) K 4 -stimulated release of glutamate in vivo has been shown to be increased from the brains of portacaval shunted rats measured using either the cortical cup technique [38] or in vivo cerebral microdialysis [39], and (6) densities of 3H-glutamate binding sites are decreased in the brains of portacaval shunted rats [40] consistent with down-regulation of these sites following prolonged exposure to increased concentrations of endogenous ligand (glutamate).…”

Oxidative Stress and Mitogen-Activated Protein Kinase Phosphorylation Mediate Ammonia-Induced Cell Swelling and Glutamate Uptake Inhibition in Cultured Astrocytes

“…Thus, whereas total brain glutamate levels are decreased in various models of HE (Hindfelt et al, 1977;Bosman et al, 1990;Dejong et al, 1992), extracellular glutamate levels are consistently increased in rat models of acute liver failure (Moroni et al, 1983;Tossman et al, 1987;de Knegt et al, 1994). Ammonia has been shown to suppress high affinity glutamate uptake (Bender and Norenberg, 1996).…”

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“…Reductions in brain GS activity, as observed in the present and a previous study (Girard et al, 1993), would therefore be expected to result in decreased astrocytic glutamate uptake following PCA. In favour of this possibility, several reports describe increases of extracellular brain concentrations of glutamate in the brains of PCA rats (Moroni et al, 1983;Tossman et al, 1987), a finding which is consistent with diminished astrocytic uptake in the brains of these animals.…”