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  • MEL-14  (1)
  • gamma-aminobutyric acid  (1)
  • phorbol myristate acetate  (1)
  • 1
    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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  • 2
    ISSN: 1573-2568
    Schlagwort(e): Leu-8 ; MEL-14 ; primary biliary cirrhosis ; phorbol myristate acetate ; protein kinase C
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The majority of circulating CD4+ T cells express the Leu-8 peripheral lymph node homing receptor, and these cells have previously been shown to have suppressor-inducer and suppressor function. In the present study, it was found that CD4+, Leu-8+ T cells from patients with primary biliary cirrhosis (PBC) have a significantly (P〈0.01) lower proliferative response when stimulated with phytohemagglutinin (PHA), concanavalin A (Con A), or pokeweed mitogen (PWM) compared to normal controls. The proliferative response of CD4+, Leu-8− T cells was similar in patients and controls. However, the proliferative responses of CD4+, Leu-8+ from patients with PBC was normal when cells were stimulated with PHA, Con A, anti-CD3 monoclonal antibody, or ionomycin in combination with phorbol myristate acetate (PMA). CD4+ T cells from patients with PBC mediated normal helper function for PWM-stimulated immunoglobulin synthesis at high T/B ratios and their regulatory function was similar to that of normal CD4+ T cells that had been irradiated to inactivate their suppressor activity. When CD4+ T cells from patients with PBC were precultured with the combination of Con A and PMA, they mediated potent inhibitory activity similar to that of normal CD4+ T cells. Thus, CD4+, Leu-8+ T cells from patients with PBC have a defect of proliferation and suppressor function that is reversed by coculture with PMA. This finding suggests that impairment of a PMA-inducible lymphocyte activation pathway contributes to abnormal lymphocyte function in PBC.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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