摘要:

Abstract—The effects of various cations and cholinergic ligands on the rate of α‐bungarotoxin‐acetylcholine receptor complex formation has been studied by means of a DEAE‐cellulose disk assay technique. The reaction rate is reduced to one half the initial rate in the presence of 2·5 · 10−6macetyleholine. a value close to the observed KDof ACh measured by equilibrium dialysis. Inhibition constants of about 5 mM were obtained for most monovalent cations whereas divalent cations gave inhibition constants of 0·05‐0·2 mm. The rate and extent of toxin‐receptor complex formation was also investigated as a function of hydrogen ion concentration; the rate of formation reaches a maximum at pH 7·5 and a group with a pK about 6 inhibits toxin binding to the receptor when protonated.These data can be correlated with the observed effects of inorganic cations on the binding of cholinergic ligandsin vivoat the neuromuscular junction. Given the affinities of the individual cations, it is possible to predict how the apparent affinity of a cation‐sensitive cholinergic ligand will change with variations

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1974.tb04383.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

Abstract—Acute injections of LSD (2 × 500 μg/kg) to rats resulted in evidence of a reduced 5‐hydroxytryptamine (5‐HT) turnover in all brain areas studied. In contrast, a much smaller dose of LSD (20 μg/kg) repeated daily for 1 month produced a significantly reduced turnover only in the midbrain area. The pons/medulla and forebrain areas showed small and not statistically significant increases in 5‐H

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1974.tb04384.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

Abstract—An electrophoretic investigation in acrylamide gels of 5‐hydroxytryptophan decarboxylase, obtained mostly from mouse, rat, and beef brain and also from beef and human liver, showed electrophoretic differences between species. With the exception of the rat, only one molecular species was found (the same in beef brain and liver). In the rat, polymers form spontaneously and are, at least in part, disaggregated by urea and by triton. Mouse‐rat or beef‐rat molecular hybrids form in the admixtures. No electrophoretic differences were found in five mice strains that were investigated. Techniques of electrophoretic analysis and of assay of 5‐hydroxytryptophan decarboxylase are described, which can be easily applied to other enzymes, provided a substrate is available in radioac

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1974.tb04385.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

Résumé—Au cours d'une période de stimulation, la réponse électrophysiologique de l'organe électrique évolue en trois phases successives: décroissance, palier, décroissance. Le taux d'acétylcholine (ACh) totale baisse durant la première décroissance. Il augmente pendant le palier, pouvant atteindre et même dépasser sa valeur initiale. Une nouvelle baisse de ce taux coïncide avec la dernière phase décroissante. Ces premières variations du taux d'ACh ne concernent que le compartiment libre’ ou disponible qui est défini dans le texte. Les corrélations décrites entre l'évolution de la décharge et celles de l'ACh ont été observées constamment dans différentes conditions de stimulation,in vivoetin vitro, aux fréquences de 1, 5 et 10/s. Une réduction de la température abrège et abaisse le palier de la réponse électrophysiologique, elle diminue la remontée de l'ACh disponible. Les premières variations de l'ACh disponible évoluent en fonction du temps selon un mode relativement indépendant de la fréquence de stimulation entre 1 et 10/s. Après une incubation en présence d'acétate14C‐1 qui est incorporé dans la moitié acétyl de l'ACh, le tissu est stimulé au contact du précurseur hautement radioactif. Dans ces conditions, les premières variations d'ACh disponible s'effectuent sans changement de sa radioactivité spécifique: le taux du transmetteur et sa radioactivitéévoluent parallèlement. L'ACh synthétisée pendant le palier doit par conséquent provenir d'un compartiment en équilibre avec l'ACh disponible ou du médiateur récemment libéré.Après la deuxième décroissance, la radioactivité spécifique de l'ACh disponible s'élève, traduisant l'épuisement du pool précurseur et l'incorporation de l'acétate très radioactif présent dans l'espace extracellulaire. A cette phase d'épuisement succède une utilisation de l'ACh vésiculaire stable, ou liée, qui semble alimenter le compartiment disponible. Le nombre des vésicules synaptiques comptées sur des micrographies électroniques peut alors diminuer. Si la stimulation est poursuivie encore plus longtemps, le nombre des vésicules retrouve ou même dépasse sa valeur initiale mais le taux d'ACh liée reste bas. Nous avons évalué la concentration de l'ACh dans les terminaisons nerveuses et celle de ses produits d'hydrolyse dans la fente synaptique. Cette dernière concentration, très élevée après un seul influx, pourrait être un des éléments essentiels du couplage entre la vitesse de synthèse de l'ACh disponible et celle de son utilisation.Abstract—During a period of stimulation the electrophysiological response of the electric organ shows three successive phases: decrease, plateau and late decrease. The level of total acetylcholine (ACh) diminishes during the first decrease. It increases during the plateau phase, where it may reach or even exceed the initial value. A new diminution of the ACh level coincides with the last decreasing phase. The first changes in ACh only concern the ‘free’ or available compartment, which is defined in the text. The correlations between the changes of ACh and those of the electrophysiological discharge have been consistently observed under various conditions of stimulation,in vivoandin vitro, at frequencies of 1, 5 and 10/s. When the temperature is reduced, the plateau of the response becomes lower and shorter, and the corresponding increase in ACh is smaller. The time course of the first changes in the available ACh was not modified by the frequency of stimulation between 1 and 10/s. After an incubation with [1‐14C]acetate, which is incorporated in the acetyl moiety of ACh, the tissue was stimulated in the presence of the highly radioactive precursor. Under these conditions, the first variations in the available ACh are not accompanied by any change in its specific radioactivity (RA.S), variations of the radioactive and non‐radioactive transmitter being parallel. The ACh synthesized during the plateau should therefore originate either from a pool in equilibrium with the availableACh, or from the recently released transmitter. Following the second fall of the available ACh, its specific radioactivity increases indicating a greater incorporation of the highly radioactive acetate of the extracellular space in a diminished precursor pool. After this phase, bound (stable vesicular) ACh is utilized and appears to supply the available compartment. The number of synaptic vesicles counted in electron micrographs may diminish at this stage. If stimulation is still continued, the vesicles recover or even exceed their initial number whereas bound ACh remains at a low level. An estimate has been made of the concentration of ACh in nerve terminals and its hydrolysis products in the synaptic cleft. The latter concentration, very high after only

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1974.tb04386.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

Abstract—[14C]‐Glutamate and [14C]‐glutamine were incorporated into calf brain tRNA in the presence of homologous aminoacyl‐tRNA synthetases. When the tRNAs were then deaminoacylated and chromatographed, a number of radioactive products were found in addition to the original amino acids. One of the products of glutamate transformation was identified to be glutamine. Formation of the radioactive products of glutamate in the presence and absence of tRNA indicated that glutamine was produced from glutamate at the level of the free amino acid followed by the incorporation of both substances into tRNA. Examination of the products of deaminoacylation of glutaminyl‐tRNA showed that glutamine underwent structural alterations at the level of the aminoacyl‐tRNAs to give rise to a cyclic derivative of glutarimide. This reaction was specific for glutamine, and constituted approximately 15 per cent of the total radioactivity in the deaminoacylation products of glut

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1974.tb04387.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

Abstract—The redistribution of rapidly migrating [3H]leucine‐labelled proteins was studied using double ligatures applied to the vagus nerve and single ligatures, applied to the hypoglossal nerves. Rapidly migrating proteins accumulating for 16 h proximal to a distal ligature of the cervical vagus redistributed to give a retrograde accumulation distal to a second ligature. Within 6 h a substantial redistribution occurred indicating a rapid retrograde transport. After 21 h there was a further accumulation with 70 per cent of the labelled material accumulating at the distal end of the isolated nerve segment and 16 per cent accumulating at the proximal end. It was shown that about a half of the retrograde accumulation was dependent on the distal accumulation zone. Rapidly migrating proteins accumulated distal to a ligature applied to the hypoglossal nerve 16 h after labelling of the nerve cell bodies indicating that a rapid retrograde transport of labelled macromolecules occurs from the peripheral parts of the nerve in the tongue. Labelled proteins accumulated proximal to ligatures and transections of both the hypoglossal and vagus nerve when applied 16 h after labelling of the nerve cell bodies, indicating the presence of axonal proteins, migrating at a rate of transport intermediate to that of rapidly and slowly migrating prote

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1974.tb04388.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

Abstract—The influence of insulin‐induced hypoglycemia upon carbohydrate substrates, amino acids and ammonia in the brain was studied in lightly anaesthetized rats, and the changes observed were related to the blood glucose concentration and to the EEG. Calculations from glucose concentrations in tissue, CSF and blood indicated the presence of appreciable amounts of free intracellular glucose at blood glucose concentrations above 3 μmol/g. When the blood glucose concentration fell below 3 μmol/g, there was no calculated intracellular glucose and decreases in the concentrations of glycogen, G‐6‐P, pyruvate, lactate and of citric acid cycle intermediates were observed. At blood glucose levels of below 1 μmol/g the tissue was virtually depleted of glycogen, G‐6‐P, pyruvate and lactate.When the blood glucose concentration was reduced below about 2·5 μmol/g there were progressive increases in aspartate and progressive decreases in alanine, GABA, glutamine and glutamate, and at blood glucose concentrations below 2 μmol/g the ammonia concentration increased. It is suggested that most of the changes observed can be explained as a result of a decreased availability of pyruvate and of NADH. The decrease in the concentration of free NADH was reflected in reductions of the lactate/pyruvate and malate/oxaloacetate ratios at an unchanged intracellular pH.Slow wave activity appeared in the EEG when the hypoglycemia gave rise to reduction of the intracellular glucose concentration to zero. Convulsive activity continued until carbohydrate stores in the form of glycogen and G‐6‐P were depleted. When this occurred the EEG became isoelectric. In all convulsive animals the concentration of the nervous system activity inhibitor, GABA, was decreased and stimulant, asp

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1974.tb04389.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

Abstract—Concentrations of phosphocreatine, creatine, ATP, ADP and AMP were measured in the cerebral cortex of rats during insulin‐induced hypoglycemia. Blood glucose concentrations were related to clinical symptoms in unanaesthetized animals and to the EEG pattern in paralysed and lightly anaesthetized animals. There was an excellent correlation between blood glucose concentration and EEG pattern. In animals showing a pronounced slowing of the EEG or convulsive polyspike activity for up to 20 min, there were no changes in any of the phosphates. However, after prolonged convulsive activity some animals showed clear signs of energy failure, and in all animals with an isoelectric EEG there was a major derangement of the energy state. Since the majority of those animals did not show signs of cerebral hypoxia or ischemia it is concluded that hypoglycemic coma is accompanied by substrate deficiency of a degree sufficient to induce energy depletion of brain tis

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1974.tb04390.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

Abstract—After injection of [3H]guanosine or [3H]uridine into the eye of goldfish, labelled acid‐soluble radioactivity and RNA appeared in the contralateral optic tectum. When 0·1 μg actinomycin‐D was injected into the eye 4 h before the precursor, the labelled RNA in the retina by 18 h after the injection was only 23 per cent of normal, but the acid‐soluble radioactivity in the retina and the small amount of labelled acid‐soluble material conveyed to the tectum were not significantly affected; by 15–20 days after the injection the acid‐soluble radioactivity in the retina was reduced and the amount of labelled material conveyed to the tectum, including both RNA and acid‐soluble fractions, was less than normal.When the actinomycin was injected at various times before or after the precursor and measurements were made 6 days later, it was found that the amount of labelled RNA conveyed to the tectum was maximally decreased if the inhibitor was given simultaneously with or up to 4 h before the precursor, whereas the amount of RNA was normal if the incorporation of the precursor had been allowed to proceed for 12 h before the inhibitor was given. This result would be consistent with the view that much of the RNA conveyed to the tectum had been synthesized in the retina within 12 h of the injection of the precursor, and had then presumably been axonally transported in the optic nerve to the tectum. However, since the acid‐soluble material conveyed to the tectum was also reduced as a result of the actinomycin treatment, the results of these experiments with actinomycin do not unequivocally rule out the possibility that the RNA appearing in the tectum had been locally synthesized from the axonally transported acid‐soluble material. In the retina, both the labelled RNA and acid‐soluble fractions were reduced, to about 15 and 60 per cent of normal, respectively, without any relationship to the time between the injection of inhibitor and precursor. The discrepancy between the effects of the labelling of the retina and the labelling of material conveyed to the tectum could be correlated with the fact that the actinomycin caused severe damage to the retinal receptor cells, while leaving the ganglion cells relatively intact. The more pronounced effect of actinomycin on the receptor cells could in turn be correlated with the fact that these cells had a higher rate of RNA synthesis than the ganglion cells. This was demonstrated autoradiographically by the higher rate of incorporation of [3H]uridine into the receptor cells.Intracranial injection of actinomycin did not affect significantly the amount of labelled RNA conveyed to the tectum, which would argue against the local synthesis of this RNA. It is not certain, however, that the actinomycin penetrated deeply enough into the

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1974.tb04391.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

Abstract—Intact and dissociated dorsal root ganglia from 8‐day chick embryos were examined for their ability to incorporate radio‐precursors into RNA and protein in unsupplemented medium or in medium supplemented with Nerve Growth Factor, insulin, Concanavalin A, fetal calf serum, or several combinations of such agents. In the absence of any agent, incorporation into RNA and protein declined with time. All four agents maintained or improved the initial incorporation rates, and optimal doses were determined in each case. Different combinations of two agents led to potentiated, full or partially additive, or inhibited effects; in particular, NGF promoted incorporation even in conjunction with insulin (additive) or serum (potentiating). Several differences were noted between the responses of intact and of dissociated ga

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1974.tb04392.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY