Thiopental inhibition of gamma-aminobutyrate transminase in rat brain synaptosomes.
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Biomedical subjects
Publications and source records attributed to S C Cheng.
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Sodium nitroprusside (SNP) is rapidly metabolized to cyanide (CN) and thiocyanate (SCN). The authors determined the rates of CN and SCN production during SNP infusion sufficient to maintain blood pressure at 80 per cent of baseline in the dog awake and during halothane anesthesia. Each dog served as its own control. The endogenous whole-blood CN concentration was significantly lower in anesthetized dogs (0.6 nmol/ml) than awake dogs (1.8 nmol/ml). CN concentration increased similarly during SNP infusion in awake (4.5 nmol/ml) and anesthetized dogs (2.3 nmol/ml). In another group of dogs, whole-blood CN concentration decreased significantly due to halothane anesthesia. The regression coefficient was -0.21 nmol CN/ml/hr. There was no significant difference in plasma SCN concentration following infusion of SNP in both awake (33 nmol/ml) and anesthetized dogs (26 nmol/ml). The cause of this decreased blood CN concentration with or without SNP infusion during halothane anesthesia is not known.
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Effects of spironolactone, canrenone and canrenoate-K on adrenal cytochrome P450 (P450) and corticosteroid biosynthesis were examined by studying difference spectra, P450 reduction and corticoid hydroxylation in mitochondrial preparations isolated from zona fasciculata and zona glomerulosa of bovine adrenals and from adrenal adenoma and hyperplastic adrenal cortex removed from patients with hyperaldosteronism. All three agents bound to P450 producing type I difference spectra and underwent hydroxylation. They all inhibited 11beta-hydroxylation in bovine adrenal at 30 muM and higher concentrations. Canrenone, the most potent inhibitor, blocked enzyme activity by 60% at a concentration of 60 muM. Spironolactone stimulated P450 reduction. The order of potency of inhibition was found to correlate with the order of affinity of these agents for P450. 11beta-Hydroxylase in human adrenal appeared to be less sensitive to canrenone. All three agents or their hydroxylated metabolites blocked 18-hydroxylation in bovine adrenal at lower concentrations. Canrenoate-K, being the most effective, inhibited 52% at 20 muM. Low concentrations of canrenone (2.5-5.0 muM) were without effect on 11beta-hydroxylase but markedly inhibited 18-hydroxylation (62-76%) in hyperplastic human adrenals. The inhibitors produced mixed type inhibition of 11beta-hydroxylation and competitive type inhibition of 18-hydroxylation. These findings indicate that at low concentrations spironolactone and its major metabolites, canrenone and canrenoate-K, or their hydroxylated metabolites, can directly interfere with the biosynthesis of aldosterone in bovine and certain human adrenal cortical tissue.
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Major inhalational anesthetics cause inhibition in the electron transport chain in the region of Complex I resulting in decreased oxygen utilization, inhibition of metabolism of NAD-linked substrates, but not of succinate, inhibition of mitochondrial calcium uptake, and depression of synaptic transmission because of postulated changes in ACh sensitivity or GABA inhibition. Many cellular metabolic effects in CNS and other tissues are secondary to the above. Many metabolic changes noted with anesthetics occur subsequent to activation of the sympathetic nervous system either directly by the anesthetic or by surgical stimulation in the presence of light anesthesia. Many important studies remain to be done.
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