Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to assess the possible loci of action of neuroleptics in blocking the acquisition of a one-way conditioned avoidance response, microinjections of three neuroleptics and seven putative neurotransmitters were made into several brain regions and their effects on this behavior were assessed. When injected into the amygdala, the ED50 values for haloperidol (0.128 nmol), chlorpromazine (1.04 nmol) and thioridazine (1.41 nmol) were appropriate in relation to their clinical potency. Injections of neurotransmitters were without effect except in a few cases. Most significantly, the intra-amygdaloid administration of glutamate diethyl ester (an antagonist at quisqualate-type receptors) produced a blockade of avoidance acquisition which, as in the case of the neuroleptics, was not diminished by pretreatment with atropine. Following intraperitoneal injection of chlorpromazine, a statistically-significant blockade of avoidance acquisition and of glutamate, released from slices of amygdala, was obtained at doses of 2 mg/kg or more. With haloperidol, comparable behavioral effects and release of glutamate were found at doses of 0.05 mg/kg or more. The depression of release of glutamate from amygdaloid slices could be attributed to glutamate derived from glutamine. These data suggest a possible role for glutamatergic transmission in the effects of neuroleptics.
 ...
PMID:Potential locus and mechanism of blockade of conditioned avoidance responding by neuroleptics. 614 66

Production of glutamine synthetase in Saccharomyces cerevisiae is controlled by three regulatory systems. One system responds to glutamine levels and depends on the positively acting GLN3 product. This system mediates derepression of glutamine synthetase in response to pyrimidine limitation as well, but genetic evidence argues that this is an indirect effect of depletion of the glutamine pool. The second system is general amino acid control, which couples derepression of a variety of biosynthetic enzymes to starvation for many single amino acids. This system operates through the positive regulatory element GCN4. Expression of histidinol dehydrogenase, which is under general control, is not stimulated by glutamine limitation. A third system responds to purine limitation. No specific regulatory element has been identified, but depression of glutamine synthetase is observed during purine starvation in gln3 gcn4 double mutants. This demonstrates that a separate purine regulatory element must exist. Pulse-labeling and immunoprecipitation experiments indicate that all three systems control glutamine synthetase at the level of subunit synthesis.
 ...
PMID:Three regulatory systems control production of glutamine synthetase in Saccharomyces cerevisiae. 615 13

The temporal sequence of electrophysiological and biochemical correlates of epilepsy induced by systemic injection of kainic acid (15 mg/kg i.p.) was investigated in male rats. A significant decrease in the hippocampal concentration of glutamate and aspartate was observed 20 min after the injection. These decreases preceded both electrographic and behavioral manifestations of epilepsy, thus suggesting a causal relationship between acidic amino acid changes and the genesis of kainate-induced hyperactivity. About 30-45 min after kainate injection, a decrease in glutamate, aspartate, glycine and taurine and no change in GABA concentration were observed. Bioelectrical activity, recorded in the regio inferior (CA3) of the hippocampus or in the fascia dentata revealed the presence of high frequency bursts separated by a long-lasting depression of discharge. About 55-75 min after the injection, the number of spikes in each burst increased and the duration and frequency of interictal pauses decreased. This stage was characterized by a decrease in glutamate and aspartate, restoration to normal of glutamine, glycine and taurine and a decrease in GABA.
 ...
PMID:Altered time course of changes in the hippocampal concentration of excitatory and inhibitory amino acids during kainate-induced epilepsy. 647 26

The release of [3H] gamma-aminobutyrate (GABA) neosynthesized from [3H]glutamine was estimated in one substantia nigra and in the ipsilateral thalamus of halothane-anesthetized cats by perfusing a [3H]glutamine-enriched physiological medium through a push-pull cannula implanted in the two structures under investigation. After two hours of superfusion, muscimol (10(-6)M) was delivered through the nigral push-pull cannula for 50-60 min and local- and distal-evoked changes of [3H]GABA release were analyzed. In some experiments, changes of global neuronal activity induced by muscimol application were recorded in different thalamic nuclei, using a bipolar electrode. In a few of the above experiments, biochemical and electrophysiological determinations were simultaneously performed in the substantia nigra and the thalamus. The nigral application of muscimol (10(-6)M) induced locally an activation of the substantia nigra reticulata cells, as well as an increase in release of [3H]GABA. Distally, in the thalamus, two types of biochemical and electrophysiological responses were observed according to the localization of the tip of the push-pull cannula or the electrode. (1) An increased release of [3H]GABA and a depression of the global multi-unit cellular activity were obtained in the ventralis medialis-ventralis lateralis, the centralis lateralis and the paracentralis nuclei. These effects could reflect an activation of the GABAergic nigrothalamic neurons projecting to these different thalamic nuclei. (2) In contrast, in the medialis dorsalis paralamellar zone adjacent to the intralaminar nuclei of the thalamus, a decrease of [3H]GABA release and an activation of the multi-unit activity were obtained. These latter results may suggest either a polysynaptic response or the non-GABAergic nature of the nigrothalamic neurons afferent to the medialis dorsalis paralamellar zone.
 ...
PMID:Effects of nigral application of muscimol on release of [3H] gamma-aminobutyrate and on multiunit activity in various cat thalamic nuclei. 664 28

The amino acid and ammonia profiles in various tissues of the rat exposed to different pressures of pure oxygen have been studied. Well-defined changes in behavioral activity accompanied a profile of increasing pressure, culminating in convulsive activity in each group of exposed animals. After an initial depression of ammonia, in all tissues studied at 0.68 atm oxygen ammonia increased significantly at higher oxygen pressures. A rise in tissue ammonia took place in the absence of undue muscular activity on the part of the exposed animals. A significant increase in ammonia occurred first in brain and liver at 3.40 atm. Ammonia concentration was high in all tissues after convulsions occurred at 4.08 atm. Between 0.68 and 2.72 atm oxygen, tissue ammonia concentration was generally low and brain glutamate and gamma-aminobutyric acid were high. At pressures higher than 2.72 atm oxygen, tissue glutamate declined and glutamine increased. Alanine became significantly elevated in serum and muscle at high oxygen pressure, and aspartate was depressed in heart, liver, and muscle. These pressure-course experiments on ammonia accumulation in tissue confirm previous serial time course observations that ammonia accumulates in the brain and several tissues of the rat even in the absence of undue muscular activity during high-pressure oxygen exposure and is a significant factor in inducing convulsions.
 ...
PMID:Tissue ammonia and amino acids in rats at various oxygen pressures. 683 41

The addition of many oxidizable substrates to the medium of incubating rat renal slices decreases ammoniagenesis from glutamine and glutamate. Interestingly, lactate and beta-hydroxybutyrate depress ammoniagenesis less in renal slices from acidotic rats compared with normal-control rats. In this study, the effects of an expanded panel of substrates on ammoniagenesis in kidney slices from control and acidotic rats were followed to discern patterns of inhibition. In addition to lactate and beta-hydroxybutyrate, acetate, pyruvate, and perhaps acetoacetate caused relatively less depression of ammoniagenesis in acidotic slices. Citrate, succinate, fumarate, octanoate, and alpha-ketoglutarate decreased ammoniagenesis to the same extent or more in acidotic slices compared with that in normal-control slices. Glycerol had little effect on ammoniagenesis under either condition. From the substrates tested, it can be generalized that those outside the TCA cycle (with exception of octanoate) depress ammoniagenesis less during acidosis, while those in the TCA cycle depress ammoniagenesis equally or even more during acidosis. We hypothesize from the pattern of our results that changes in renal intermediary metabolism at or before citrate formation occur during acidosis and are important regulatory mechanisms for ammoniagenesis.
 ...
PMID:The regulation of renal ammoniagenesis in the rat by extracellular factors. III. Effects of various fuels on in vitro ammoniagenesis. 688 70

L-Proline and some of its analogs have been shown to prevent spreading depression (SD) in the chick retina at relatively low concentrations and to impair memory processing without provoking toxic or electrophysiological disturbances. Both effects are hypothesized to be caused by inhibition of the effects of glutamate released into the extracellular space. L-Proline, its D-enantiomer, six proline analogs including two homologs (L-azetidine-2-carboxylic acid and DL-pipecolic acid), and five other compounds were examined for their effects on spreading depression and their amnestic and electrophysiological effects. L-Proline, L-baikiain, DL-3,4-dehydroproline, and L-4-hydroxyproline all reduced the incidence of SD in the chick retina and proved to be amnestic. D-Proline, L-pyroglutamic acid, L-azetidine-2-carboxylic acid, DL-pipecolic acid, L-glutamic acid diethylester, L-isoleucine and L-norleucine neither depressed SD nor caused retrograde amnesia. L-Prolyl-L-proline and L-glutamine did not depress SD at low concentrations but had significant amnestic effects. None of the listed compounds induced EEG disturbances. Implications for memory mechanisms are discussed in the light of these results.
 ...
PMID:Amnestic potency of proline analogs correlates with anti-spreading depression potency. 719 Feb 93

In an unselected consecutive series of 126 children, 1-15 years, seen in a paido-psychiatric outpatient service for various complaints, and in a large extent diagnosed as suffering from childhood depression, 61 of them (48.41%) presented, among other symptoms, a marked susceptibility to infective respiratory diseases. A pharmacotherapy carried out by means of GABAergic drugs (l-glutamine, pyridoxine and a benzodiazepine), besides improving both the alleged complaint and other symptoms of depression, made noticeable improvement or disappearance of this susceptibility in 40 out of the 42 subjects who came back for check-up. Susceptibility to infective respiratory diseases is believed due both to impairment of GABAergic mechanisms as first modulators of hypophysis secretion and adrenergic and cholinergic responses, and to a lack of l-glutamine as a donor of essential C atoms for the construction of proteins and nucleic acids.
 ...
PMID:Susceptibility to infective respiratory diseases in depressed children. Epidemiological survey of 126 subjects, clinical-therapeutic report of 61 cases. 733 41

Succinylated Acinetobacter glutaminase-asparaginase (SAGA) has broader antitumor activity than Escherichia coli L-asparaginase in experimental systems; moreover, drug resistance does not develop in tumor cell lines initially sensitive to this enzyme. We have investigated the pharmacology and toxicology of SAGA after both single-dose and serial daily dose injections in 20 adult patients. Glutaminase activity in plasma after i.v. injection of single doses did not follow simple first-order kinetics (half-life during the initial 24 hr was 21 +/- 9 hr. A linear relation was observed between increasing doses of SAGA and resultant levels of plasma enzyme activity and blood glutamate. Assay of whole blood which had been deproteinized immediately following phlebotomy showed that single doses of SAGA lowered glutamine only transiently to nondetectable levels; serial daily doses were required to achieve and maintain continuous glutamine depletion. Reversible depression of the central nervous system, ranging from encephalopathy to coma, occurred in a dose-related manner and was dose limiting. Other prominent reactions included respiratory alkalosis, hyperglycemia, nausea, and vomiting. Transient antitumor effects were noted in two patients with solid tumors and in two patients with leukemia. SAGA causes considerable neurotoxicity in adults which requires close patient monitoring. Phase II studies in leukemic patients are in progress.
 ...
PMID:Phase I evaluation of succinylated Acinetobacter glutaminase-asparaginase in adults. 743 89

Spreading depression, which can be evoked by a variety of stimuli both in vitro and in vivo, is associated with profound changes in extracellular ion concentrations and enhanced release of neurotransmitter amino acids. We have observed a transient spontaneous release of amino acids in slice preparations obtained from rat cerebellum, striatum and hippocampus; this phenomenon has similar properties to stimulus-evoked spreading depression. Aspartate, glutamate, glutamine, serine, glycine and gamma-aminobutyric acid (GABA) release were potentiated during these episodes in all three brain regions, with a variable effect upon taurine release. When compared to glutamate release, a consistently high release of aspartate, glycine and serine was observed. Amino acid release, evoked by whole slice depolarization using veratridine (10-25 microM) or elevated potassium (35-60 mM) consistently enhanced glutamate release, and to a lesser extent aspartate release, but had negligible effect upon the other amino acids. Thus, the release profiles for spontaneous and depolarization-evoked release are markedly different. We suggest that the spontaneous release observed in brain slices represents a spreading depression-like phenomenon; the putative roles of the amino acids are discussed.
 ...
PMID:A comparison between the stimulated and paroxysmal release of endogenous amino acids from rat cerebellar, striatal and hippocampal slices: a manifestation of spreading depression? 756 53


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>