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  • flunitrazepan binding  (1)
  • gamma-aminobutyric acid  (1)
  • 1
    ISSN: 1573-7365
    Schlagwort(e): benzodiazepine receptors ; flunitrazepan binding ; galactosamine ; hepatic encephalopathy ; triton X-100 ; receptor solubilization ; synaptic membrane
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Increased benzodiazepine (BZ) receptor density has been reported in brains of rabbits with hepatic encephalopathy (HE) due to galactosamine (GalN)-induced fulminant hepatic failure (FHF). These data were generated using detergent-Triton X-100-treated neural membranes. While performing further studies it was noted that the increase in BZ receptor density was not demonstrable when Triton X-100 preparation was not employed. Accordingly the binding of [3H] flunitrazepam, a BZ ligand, to neural membranes from cortices of normal rabbits and rabbits with HE due to (GalN)-induced FHF was studied with and without detergent preparation. Scatchard plot analysis of the binding data indicated that when no detergent was employed, the apparent affinity and density of BZ receptors were similar for control membranes and membranes from animals in HE. BZ receptors from animals in HE were shown to be more resistant to solubilization by Triton than control membranes. These findings (a) afford a potential explanation for the apparent increase in density of BZ receptors in this model when Triton treatment of neural membranes is utilized and (b) suggest that recent evidence for increased GABAergic tone in the syndrome of HE is not dependent on an increased density of BZ receptors.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1573-7365
    Schlagwort(e): hepatic encephalopathy ; gamma-aminobutyric acid ; chloride channel ; synaptoneurosomes ; benzodiazepine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The functional activity of the gamma-aminobutyric acid (GABAA) receptor-chloride ionophore complex was studied in rats with hepatic encephalopathy (HE) secondary to thioacetamide-induced fulminant hepatic failure (FHF). Muscimol stimulation and benzodiazepine potentiation of GABA receptor-mediated36Cl− uptake into cerebral cortical synaptoneurosomes was compared in HE and control rats. [3H]Flumazenil binding assays were conducted to determine whether the levels of endogenous benzodiazepine-like ligands in extracts of cortex were increased with stages of encephalopathy in this animal model of HE. In both control and HE rats maximal uptake of36Cl− via the GABAA receptor complex occurred at muscimol concentrations of 30μM. Potentiation of muscimol-stimulated36Cl− uptake into synaptoneurosomes by diazepam (5μM) was equivalent in both groups. Aqueous extracts of proteolytically digested homogenates of cerebral cortices prepared from control and HE rats were effective in stimulating36Cl− uptake into synaptoneurosomes. Alkaline organic extracts of proteolytically digested homogenates of cerebral cortices from HE rats were more effective than corresponding extracts from controls at inhibiting the binding of [3H]flumazenil. Inhibition of [3H] fumazenil binding by organic extracts derived from the cerebral cortices of HE rats did not increase with progression of encephalopathy. The results show that muscimol-stimulated36Cl− uptake into synaptoneurosomes and, consequently, GABAA receptor-mediated chloride channel function are not significantly altered in the model of HE studied and are consistent with the hypothesis that HE results in an increased availability of one or more endogenous ligands which can augment GABA receptor-gated chloride conductance.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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