CHARACTERISTICS OF DICARBOXYLIC AMINO ACID TRANSPORT BY RABBIT INTESTINAL BRUSH-BORDER MEMBRANE VESICLES

Comparisons among occurrences of a transport system in the intestinal and renal brush-borders and in other cells prove informative     

1-肉桂基-4-(2,3,4-三甲氧基苄基)-四氢吡嗪盐酸盐对大鼠心肌缺血再灌性心律失常的保护作用

采用整体大鼠心肌缺血再灌注模型，观察1-肉桂基-4-(2,3,4-三甲氧基苄基)-四氢吡嗪盐酸盐（CTTP）对缺血再灌性心律失常的保护作用. 于结扎前3 min, CTTP 2.5或5 mg·kg^-1 iv，可显著降低缺血再灌损伤引起的室性心律失常发生率，缩短持续时间；能明显减少心肌谷草转氨酶，肌酸激酶和乳酸脱氢酶释放量；升高超氧化物歧化酶活性，减少脂质过氧化反应代谢产物丙二醛含量. 提示CTTP抗心肌缺血再灌注心律失常的作用，可能与降低心肌脂质过氧化和增强氧自由基清除酶的活性有关.     

Regulation of glutamate biosynthesis and release in vitro by low levels of ammonium ions

The content and release of endogenous amino acids from isolated rat hippocampal slices were measured. The tissue was perfused with control media and pulsed with high potassium media in order to induce synaptic release. Pathophysiological concentrations of ammonium ions (3--5 mM) were added to the control medium for 60 min prior to the induced release. Amino acids belonging to the putative transmitter group were released extensively during potassium perfusion and, except for glutamate, even after ammonium ion perfusion. The spontaneous secretion of glutamate increased, however, slowly after the addition of ammonia. The incorporation of 14C from radiolabelled glucose and acetate into the amino acid fraction was studied in the presence of ammonia-containing media. Glucose was utilized to a moderately increasing extent, but acetate-derived radioactivity was strikingly decreased in the amino acid fraction during ammonia perfusion. The decreased acetate incorporation into amino acids was mainly due to an inhibition by ammonia of the accumulation of acetate by the CNS tissue.     

Development of tissue resistance to toxic effects of chemicals

Evidence has been presented from both the published literature and the author's own work that after repeated administration of various chemicals which induce degenerative changes, resistance develops in the target tissue to the toxic effects. Such a resistance develops only after an induced lesion, and it is not specific to the inducing agent, but extends to agents causing similar lesions. The resistance lasts during the period of exposure to the noxious agent and for varying times thereafter. It is looked upon as an adaptation mechanism to the adverse environment; thus it is of epidemiological interest. This phenomenon is of significance also in the safety studies of chemicals. The present practice of performing histopathology examinations solely in prolonged dosing studies may overlook what happened in the early stages of the exposure to potentially toxic agents. The resistance is also of clinical interest, since the toxic effect may not manifest in long-term therapy even though the pharmacologic effect does not diminish. The continuing pharmacologic effect implied that the phenomenon is not related to a pharmacokinetic change. Apart from this, its mechanism has not been established.     

Immediate and delayed effects of in vitro ischemia on glutamate efflux from guinea-pig cerebral cortex slices

Immediate and delayed effects of glucose deprivation, oxygen deprivation (hypoxia) and both oxygen and glucose deprivation (in vitro ischemia) on glutamate efflux from guinea pig cerebral cortex slices were studied. Immediate effects were evaluated by measuring changes of glutamate efflux during the metabolic insults. Delayed effects were evaluated by measuring the response of the tissue to a 50 mM KCl pulse applied 60 minafter the metabolic insults. Deprivation of glucose in the medium did not induce either immediate or delayed effects, while hypoxic condition produced an immediate slight stimulation of glutamate efflux without any delayed effect. Conversely, in vitro ischemia produced both immediate and delayed effects on glutamate efflux. During in vitro ischemia glutamate efflux dramatically increased in a calcium-independent and tetrodotoxin-sensitive manner; this effect was potentiated by a low sodium containing medium. The blockade of the sodium/potassium ATP_ase exchanger by ouabain caused a glutamate outflow similar to that induced by in vitro ischemia. On the whole, these data demonstrate the central role played by the sodium electrochemical gradient and by the membrane glutamate uptake system in the glutamate overflow induced by in vitro ischemia. Moreover, in slices previously exposed to both oxygen and glucose deprivation the effect of KCl on glutamate efflux was potentiated. This in vitro ischemia-induced delayed potentiation of neurotransmitter efflux, until now unreported in the literature, was found to be selectively restricted to glutamatergic structures and to be mainly due to an enhancement of the exocytotic component of glutamate release. © 1997 Elsevier Science B.V. All rights reserved.     

Localization of the glutamate transporter protein GLAST in rat retina

Glutamate is a neurotransmitter in retina. Glutamate transporter proteins keep the resting extracellular glutamate concentration low. This is required for normal neurotransmission and prevents the extracellular concentration of glutamate from reaching toxic levels. Here we describe the light and electron microscopic localization of the glutamate transporter protein GLAST in rat retina using an antibody raised and affinity purified against a peptide corresponding to amino acid residues 522–541. The strongest immunocytochemical labelling was observed in the outer plexiform layer, ganglion cell layer, and optic disc. GLAST was found in Müller cell processes in all retinal layers, notably ensheathing the photoreceptor terminals in the outer plexiform layer, and in astrocytes close to vessels in the inner retina and optic disc. No labelling was observed in neurons. The electrophoretic mobility of GLAST in retina was similar to that in cerebellum. In conclusion, the findings are in agreement with those reported by Derouiche and Rauen [7], except that we did not detect any GLAST in the retinal pigment epithelium.     

Glutamic acid decar☐ylase activity decreases in mouse neocortex after lesions of the basal forebrain

Glutamic acid decar☐ylase (GAD) activity was measured in the cerebral cortex of animals after acute and chronic lesions to basal forebrain cholinergic nuclei. Such lesions were shown to result in an extensive depletion of cholinergic markers in parietal cerebral cortex. A statistically significant 30% decrease in GAD activity was first detected at 6 weeks postlesion and was still measurable 8 months after the lesion. These results suggest that cholinergic inputs to cortex indirectly or directly influence GABAergic transmission in cortex.     

Nitric oxide reduces hypophagia induced by threonine free diet in the rat

Food intake and concentrations of glutamic (GLU) and aspartic (ASP) acids in the nucleus accumbens were monitored in male Sprague–Dawley rats fed a threonine free diet. These variables were measured before and after an intracerebroventricular injection of 20 nmole nitroprusside (NP), a non-enzymatic nitric oxide donor. The same variables were also monitored in: (a) rats fed a threonine free diet and injected with saline; (b) animals fed a standard diet and injected with nitroprusside; (c) rats fed a standard diet and injected with saline. The results showed that the threonine-free diet reduced food intake and GLU and ASP concentrations in the accumbens. NP reduced the hypophagia, but it did not change GLU and ASP levels in rats fed the threonine-free diet. In animals fed the standard diet, NP increased GLU and ASP concentration, and food intake. No change was found in the animals with saline injection. These findings suggest that nitric oxide reduces the hypophagia in the rats fed a threonine-free diet. The lack of increase in GLU and ASP concentration in the nucleus accumbens of the hypophagic rats indicates that NP acts on hypophagia independently by GLU and ASP.     

An improved in vitro immunization procedure for the production of monoclonal antibodies against neural and other antigens

A simplified in vitro immunization procedure has been developed for the production of monoclonal antibodies against a variety of neural antigens. The procedure, which can be applied to both soluble and membrane-bound antigens, involves the addition of an adjuvant peptide, N-acetylmuramyl-l-alanyl-d-isoglutamine, and has been found to improve all fusion parameters.     

Semichronic oral toxicity of cadmium: 1. Studies on rats

Cadmium (in the form of CdCl₂) was fed to groups of 20 male and 20 female rats each over a period of 3 months in concentrations of 0, 1, 3, 10 and 30 ppm. Appearance, behaviour, food consumption, growth and mortality of the treated rats of all groups were not affected during the 3-month period. The cadmium concentrations did not cause blood, liver or kidney damage. The systolic blood pressure of the treated animals was not increased. Autopsies and histopathological investigation of the animals showed no sign of any alterations. Cadmium accumulated dose-dependently in the kidneys and liver. Concentrations of cadmium up to 30 ppm in their feed were tolerated by rats over a period of 3 months without harm.