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

Structure-activity of primary afferent depolarising action (PAD) mediated by gamma-aminobutyrate (GABA) analogues suggests a difference between subsynaptic receptors located at fibre terminations within the dorsal horn and axonal receptors which are distributed throughout non-synaptic regions. The interaction of the bicuculline-sensitive GABA receptor (GABA A) ionophore complex with barbiturates and benzodiazepines suggests that at least three binding sites are required to explain the independent GABA-mimetic, GABA-potentiating and picrotoxin-reversing effects of such agents. Difficulties with explanation of the depressant effects of baclofen on spinal transmission, in terms of the bicuculline-resistant GABA (GABA B) receptor hypothesis, are mentioned. Glutamate-induced PAD of low threshold afferents is mediated indirectly through release of potassium. However, such terminals possess receptors (possibly autoreceptors for L-glutamate), activated by (+)2-amino-4-phosphonobutyrate, which cause depression of transmitter release. Primary afferent C-fibres possess receptors which are selectively activated by kainate and which mediate picrotoxin-resistant PAD. Such receptors may be involved in the presynaptic conditioning of C-fibre transmitter release. The peripheral terminals of vestibular primary afferents, in amphibia, possess excitatory amino acid receptors which are probably activated by the transmitter released from hair cells.
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PMID:Pharmacology of amino acid receptors on vertebrate primary afferent nerve fibres. 286 69

Tetanus-induced (400 Hz, 200 pulses) long-lasting potentiation of the stratum radiatum-evoked CA1 population spike in hippocampal slices is not accompanied by any change in Na+-independent [3H]glutamate binding sites. Homosynaptic depression that occurs subsequent to either a low frequency tetanus (20 Hz, 600 pulses) or a transient exposure to Cl(-)-free (containing NO3-) medium is associated with an elevation in the amino acid binding. [3H]Glutamate uptake into slices was decreased following a high frequency (400 Hz, 200 pulses) tetanus but in the majority of cases was increased following a low frequency (20 Hz, 600 pulses) tetanus to stratum radiatum. When the high frequency tetanus was given in the absence of extracellular Ca2+, there was a further reduction in [3H]glutamate uptake.
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PMID:Tetanic stimulation-induced changes in [3H]glutamate binding and uptake in rat hippocampus. 287 13

This study evaluated the role of excitatory amino acid (EAA) receptor activation in spreading depression (SD), using the in vitro turtle cerebellum as a model system. SD was triggered by electrical stimulation or by elevated K+ after the cerebellum had been conditioned for at least 30 min with physiological saline in which most of the chloride had been replaced by propionate. SD was recognized as a transient (1-3 min) negative shift of extracellular potential accompanied by depression of evoked potentials (15-30 min) and an increase of extracellular K+ up to 60 mM, which spread across the cerebellum at rates of 1-7 mm/min. SD usually commenced in the granular layer, which apparently contains the 3 major EAA receptor subtypes, quisqualate, kainate and N-methyl-D-aspartate (NMDA), then subsequently spread to the molecular layer, which is largely free of NMDA receptors. Glutamate, aspartate, NMDA, kainate and quisqualate all triggered SD. Kynurenic acid and 2-aminophosphonovaleric acid (APV) inhibited SD under certain conditions further suggesting involvement of EAA receptors. The initiation of SD was blocked by high Mg2+ and facilitated in low extracellular Mg2+, which also eliminated the delay in molecular layer SD onset. Our data suggest that no one EAA receptor subtype is singly responsible for SD.
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PMID:Quisqualate, kainate and NMDA can initiate spreading depression in the turtle cerebellum. 290 24

Transient global amnesia has been explained by epileptic mechanisms or transient ischemic attacks affecting the hippocampus. None of these two mechanisms appear likely. The animal experimental phenomenon entitled spreading depression of cortical electrical activity (SD) or spreading depression of Leao has been implicated in migraine pathogenesis and may be relevant to transient global amnesia. In experimental animals, SD in the hippocampus causes a temporary functional ablation lasting minutes to hours with full functional recovery. Glutamate, which is present in large amounts in the hippocampus, may experimentally elicit spreading depression, and strong emotional events may possibly liberate glutamate and bring about this reaction in human patients.
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PMID:Leao's spreading depression in the hippocampus explains transient global amnesia. A hypothesis. 370 31

The effect of acute hypoxia on adenine nucleotides, glutamate, aspartate, alanine and respiration of heart mitochondria was studied in rats. The losses of intramitochondrial adenine nucleotides (ATP+ADP+AMP) during hypoxia were related to depression of state 3 respiration supported by glutamate and malate, as well as decrease in uncoupled respiration. Hypoxia had less prominent effect on succinate-dependent state 3 respiration. Non-phosphorylating (state 4) respiratory rates and ADP/O ratios were slightly affected by oxygen deprivation. Glutamate fall in tissue and mitochondria of hypoxic hearts was concomitant with significant increase in tissue alanine and mitochondrial aspartate. The losses of intramitochondrial ATP and respiratory activity with NAD-dependent substrates during hypoxia were related to a decrease in mitochondrial glutamate. The results suggest that hypoxia-induced impairment of complex I of respiratory chain and a loss of glutamate from the matrix may limit energy-producing capacity of heart mitochondria.
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PMID:Adenine nucleotides, glutamate and respiratory function of heart mitochondria during acute hypoxia. 375 8

1. Kidneys were kept anoxic at 4 degrees , 20 degrees and 38 degrees . Mitochondria were then isolated and their oxidative phosphorylation and respiration were determined. 2. Under all conditions the rate of phosphate esterification was affected to a greater extent, or earlier, than oxygen consumption. 3. Glutamate and succinate were used as substrates. The depression of P/O ratio was greater for glutamate at 4 degrees , and for succinate at 20 degrees . 4. Anoxia abolished the inhibiting effect of fluoride on respiration. 5. Phosphate esterification, after anoxia, was higher in the presence of fluoride than its absence, whereas in control preparations they were the same. 6. The decrease in P/O ratio did not appear to be due to activation of adenosine triphosphatase, as activities of both Mg(2+)-and dinitrophenol-activated adenosine triphosphatases were decreased after anoxia.
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PMID:The effect of temperature and anoxia of kidney on the subsequent oxidative phosphorylation of mitochondria. 422 26

1. Some spontaneously firing cells in the cerebral cortex of cats can be depressed by iontophoretically applied acetylcholine or acetyl-beta-methylcholine, and this depression is antagonized by atropine. Thirteen per cent of 101 spontaneously active neurones tested were depressed by cholinergic agents and 64% were excited.2. Single stimuli applied to the adjacent cortical surface excited 132 neurones orthodromically. Acetylcholine or acetyl-beta-methylcholine depressed this synaptic firing in 18% of the cells. The depression was blocked by atropine.3. The population of neurones in which cholinergic agents depressed spontaneous or synaptic firing was located within the superficial half of the cortex.4. Glutamate-induced firing was depressed by cholinergic agents in 41% of 211 cells tested; atropine and strychnine strongly antagonized this depressant action, while dihydro-beta-erythroidine was a weaker antagonist.5. Long duration inhibition of glutamate-induced firing evoked by repetitive stimulation of the cortical surface could be blocked by atropine or strychnine in both the intact and chronically isolated cortex. This provides strong evidence for a system of intracortical cholinergic neurones which make direct inhibitory contacts with neurones in the superficial layers of the cortex.
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PMID:Acetylcholine inhibition in the intact and chronically isolated cerebral cortex. 508 32

The ability of Coxiella burnetii to couple oxidation of metabolic substrates to adenosine 5'-triphosphate (ATP) synthesis in axenic reaction buffers was examined. Pyruvate, succinate, and glutamate were catabolized and incorporated at the highest rates of 11 substrates tested. Glutamate oxidation, however, resulted in the greatest stability of the ATP pool and highest intracellular ATP levels over a 48-h period. At pH 4.5, the optimum for metabolism by C. burnetii, glutamate oxidation resulted in maintenance of the ATP pool at a concentration of approximately 0.7 nmol of ATP per mg of dry weight over a 96-h period. In the absence of substrate, ATP declined by 96 h to less than 0.01 nmol/mg of dry weight. When cells were maintained at pH 7.0 in the presence or absence of glutamate, ATP pools were considerably more stable, presumably due to the minimal metabolic activity displayed by C. burnetii at pH 7. The stability of the ATP pool reflected viability as there was greater than an 8-log decrease in viable C. burnetii after incubation for 7 days at pH 4.5 in the absence of glutamate. Viability was retained in the presence of glutamate at pH 4.5 or 7.0 in the absence of any added substrate. The stability of the ATP pool was due to endogenous synthesis of ATP coupled to substrate oxidation as shown by depression of ATP levels in the presence of inhibitors of electron transport or oxidative phosphorylation. In addition, the adenylate energy charge increased from an initial value of 0.57 to 0.73 during glutamate oxidation with a concomitant rise in the total adenylate pool size. C. burnetii therefore appears able to regulate endogenous ATP levels in response to substrate availability and pH, thus effecting a conservation of metabolic energy in neutral or alkaline environments. Such a mechanism has been proposed to play a role in the resistance of C. burnetii to environmental conditions and subsequent activation upon entry into the phagolysosome in which this organism replicates.
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PMID:Stability of the adenosine 5'-triphosphate pool in Coxiella burnetii: influence of pH and substrate. 611 46

Decreased ammonium (NH4+) excretion is associated with hyperkalemia. To determine if potassium could directly influence renal ammonia production, we investigated ammoniagenesis by rat and canine renal cortical tissues in vitro at different potassium concentrations. Renal tissue from normal and acidotic rats and normal dogs incubated in glutamine, lactate, and 7 to 10 mEq/liters of potassium or 25 mEq/liters of potassium produced significantly less ammonia than slices incubating in glutamine, lactate, and 4 to 5 mEq of potassium. Glutamate accumulation, which follows glutamine deamidation, did not decrease and even increased at 25 mEq/liters of potassium. With glutamine as the sole substrate, decreased ammoniagenesis was seen only at higher potassium concentrations (greater than 16 mEq/liters) than when lactate was also present. The depression to glutamine ammoniagenesis by high concentrations of potassium was partially obliterated in an anaerobic environment. When glutamate replaced glutamine as the precursor, renal ammonia produced by slices in 7 and 25 mEq/liters was again significantly lower than by slices incubating in 4 mEq/liters. We blocked glutamine synthesis by rat kidney slices with dl-methionine dl-sulfoximine when glutamate was the renal ammonia precursor. This essentially allows glutamate deamination to produce ammonia. Potassium depressed glutamate deamination significantly at 7 mEq/liters (decreases 13%) and at 25 mEq/liters of potassium (decreases 35%) as compared to 4 mEq/liters. The above findings are consistent with a major depressive effect of in vitro potassium on glutamate deamination in rat and canine kidneys. Other evidence, especially from rat tissue studies, suggests that potassium also may affect glutamine deamination directly. Rat kidney slices incubating in the high potassium medium of 7 mEq/liter or greater also consumed less oxygen in the presence of glutamine (P less than 0.01), oxidatively decarboxylated less glutamine (P less than 0.02) and produced less glucose from glutamine (P less than 0.01).
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PMID:Effects of in vitro potassium on ammoniagenesis in rat and canine kidney tissue. 612 28

Twenty dogs underwent 15 minutes of normothermic ischemic arrest and 30 minutes of reperfusion while on cardiopulmonary bypass. In 10 control dogs, the reperfusate blood was not modified. In 10 other dogs, the aorta was reclamped and the heart reperfused for 5 minutes with blood containing L-glutamate (0.026M). We measured coronary blood flow (microspheres), left ventricular (LV) metabolism [O2 content, adenosine triphosphate (ATP)], LV compliance (intraventricular balloon), and LV performance (balloon and Starling curves) before and 30 minutes after ischemia. Fifteen minutes of ischemic arrest produced significant depression in contractility and oxidative metabolism. L-Glutamate infusion resulted in higher oxygen uptakes (9.7 versus 6.9 cc/100 gm/min) and allowed more complete recovery of ATP content (80% versus 67%). Glutamate-treated hearts had more complete recovery in the rate of contraction, +dP/dt, (96% versus 68%), and relaxation, --dP/dt (99% versus 72%), the best recovery of compliance (74% versus 88%), and complete (100%) recovery of stroke work index (1.55% versus 0.87% gm - m/kg). We conclude that the addition of L-glutamate to reperfusate blood reverses ischemic damage. We suspect that l-glutamate acts by replenishing Krebs' cycle intermediates lost during ischemia, thereby stimulating oxidative metabolism and enhancing ATP production.
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PMID:Reversal of ischemic damage with amino acid substrate enhancement during reperfusion. 743 10


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