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[email protected]Midazolam inhibits enzyme release from neuronal and nonneuronal cells.
Midazolam, a benzodiazepine with sedative and hypnosemic effects, has been shown to interact with other drugs. Whether it also interacts with neurotransmitter/modulator release has not been investigated. This study was undertaken to assess the effects of midazolam on spontaneous and evoked release of endogenous neurotransmitters/modulators from both neuronal and nonneuronal cells. Time- and concentration-dependent effects of midazolam on release of endogenous gamma-aminobutyric acid and acetylcholine, as well as on catecholamine and serotonin release, were investigated in monolayer cultures of mouse cerebellar granule neurons, rat striatal neurons, and bovine chromaffin cells, and in one-week-old organotypic rat brain slices. Tissue concentrations of endogenous neurotransmitters/modulators were determined using prelabeling followed by membrane-permeabilized incubation, HPLC analysis, and micropartition. Release was induced by either high potassium or ionophore A23187. Midazolam (3 to 12.5 micromol/L) reduced significantly the release of catecholamines and serotonin from both rat brain slices and granule neurons, and of acetylcholine and gamma-aminobutyric acid from granule neurons. Dose-response curves were similar in both types of experiments. These inhibitory effects of midazolam seem to be specific and involve interference with some components of the secretory process. As midazolam has been shown to have membrane-stabilizing effects and to interact with other sedative/hypnosemic agents, these results indicate that it may represent a useful agent for the treatment of sleep disorders.The role of N-acetyl-beta-D-glucosaminidase in the renal brush border membrane in rats treated with glycine or glycyl-glycine.
Glycine and glycyl-glycine have been shown to cause renal toxicity and injury. These agents are metabolized in the kidney by the degradative enzyme N-acetyl-beta-D-glucosaminidase (NAG). Although these two agents have been shown to have similar effects in the kidney, there are differences in their interaction with the renal membrane. The present study was designed to determine the effect
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