Whether parenteral administration of reduced glutathione prevented ethanol induced damage to and depletion of sulfhydryl compounds in the human gastric mucosa was investigated. Ten healthy volunteers underwent endoscopy on three separate occasions. Gastric mucosal damage was induced by spraying 80% ethanol on to the gastric mucosa through the biopsy channel of the endoscope. The gastric mucosal score, total sulfhydryls, glutathione, and cysteine were evaluated in basal conditions and after ethanol administration with and without pretreatment with parenteral glutathione. Glutathione We studied 10 healthy men (age range 28-50 years, median 40 years), whose gastric mucosa was found to be normal by endoscopy and histology. There was no previous history of gastrointestinal disease or alcohol abuse nor were the subjects taking any drug. Haemorrhagic diathesis was excluded. Informed consent was obtained.Each subject underwent three endoscopies on three separate occasions 7-10 days apart. At the first endoscopy, after evaluation of the gastric mucosal score according to Agrawal, et al6 (Table I), six to eight biopsy specimens were taken from the gastric body and antrum for histological evaluation and baseline determination of sulfhydryl, glutathione, and cysteine. At the second and third endoscopy, each subject was given intravenously and in random order normal saline (100 ml/10 minute) or reduced glutathione (Tationil-Boehringer Mannheim-Italia) 2-4 g in 100 ml of normal saline/10 minute. At the end of the infusion, 40 ml of 80% ethanol were sprayed along the greater curvature of the stomach from the antrum up to the mid-gastric body, via a catheter passed through the biopsy channel of the endoscope. The endoscope was withdrawn and 30 minutes were allowed to lapse before a new endoscopy was performed to assess gastric mucosal score and to take six to eight biopsy specimens from the gastric body and antrum for sulfhydryl determination. Specimens were taken from the areas that had been exposed to ethanol but haemorrhagic or erosive lesions were avoided. The gastric mucosa was observed immediately before biopsy and a blinded endoscopist (DT) graded the mucosal findings.We also studied glutathione and cysteine plasma concentrations after an infusion of glutathione (2X4 g/10 minutes) in five subjects.
HANDLING OF BIOPSY SPECIMENSTwo specimens were fixed in 10% formalin and stained with haematoxilin and eosin for standard histology. The remaining tissue samples from each subject were combined, gently washed with ice cold saline, weighed, and immediately stored at -80°C until assay. Before assay, the tissue samples were allowed to thaw briefly and were then homogenised in 0-02 M EDTA at 4°C (final volume 500 1d) in a Potter-Elvehjem homogenising tube. The total sulfhydryl content was determined colorimetrically.' Glutathione and cysteine were measured by the method of Newton, et al,8 as described previously.9 Briefly, tissue samples were homogenised in 0-02 M EDTA at 4°C with 10 1t of 50 mM monobromo-161 on 9 May 2...
Glutamate receptor types were examined at the chromatophore synapses of the squids Alloteuthis subulata and Loligo vulgaris, where nerve-induced muscle contraction causes chromatophore expansion. Immunoblotting with antibody raised against a squid AMPA receptor (sGluR) demonstrated that AMPA/kainate receptors are present in squid skin. Application of l-glutamate evoked chromatophore muscle contractions in both ventral and dorsal skins, while NMDA was only active on a subpopulation of dorsal chromatophores. In dorsal skin, neurotransmission was partly blocked by either AMPA/kainate receptor antagonists (CNQX and DNQX) or NMDA receptor antagonists (AP-5 and MK-801) or completely blocked by simultaneous application of both classes of antagonists. In isolated muscle fibres, ionophoretic application of l-glutamate evoked fast inward CNQX- and DNQX-sensitive currents with reversal potentials around +14 mV and a high conductance to Na+. In fibres from dorsal skin only, a slower outward glutamate-sensitive current appeared at positive holding potentials. At negative potentials, currents were potentiated by glycine or by removing external Mg2+ and were blocked by AP-5 and MK-801. Glutamate caused a fast, followed by a slow, transient increase in cytoplasmic Ca2+. The slow component was increased in amplitude and duration by glycine or by lowering external Mg2+ and decreased by AP-5 and MK-801. In cells from ventral skin, no 'NMDA-like responses' were detected. Thus, while AMPA/kainate receptors mediated fast excitatory synaptic transmission and rapid colour change over the whole skin, activation of both AMPA/kainate and NMDA-like receptors in a subpopulation of dorsal chromatophores prolonged the postsynaptically evoked Ca2+ elevation causing temporally extended colour displays with behavioural significance.
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