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)

The resting pH of 7.14 +/- 0.02 within rat cortical synaptosomes is elevated in vitro by the insecticide chlordecone, in a dose-dependent manner. Chlordecone also reduces the rate of oxygen radical formation within synaptosomes. Both of these changes can also be demonstrated following in vivo treatment of rats with chlordecone (75 mg/kg body wt). Although chlordecone increases the permeability of the plasma membrane, the increase in pH observed is unlikely to be caused by this, since in vivo administration of chlordecone does not appreciably alter membrane order as evaluated by both a lipophilic probe, and a probe with an ionic segment. Another xenobiotic agent, methyl mercuric chloride, and a free radical generating system, an ascorbic acid-ferrous sulfate mixture, did not modulate synaptosomal pH, although membrane permeability was increased. Other evidence of the ability of synaptosomes to maintain homeostasis was the failure of mitochondrial inhibitors to significantly reduce pH. The drop in synaptosomal pH effected by amiloride, an inhibitor of Na+/H+ exchange, and the transient rise in pH caused by ammonium chloride further suggested that synaptosomes may be a good model in the study of the regulation of intracellular pH. The elevation of cytosolic pH, and depression of oxygen radical formation by chlordecone, may result from both the attenuation of respiratory metabolism and an impaired capacity of the plasma membrane to maintain ionic gradients.
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PMID:Changes in synaptosomal pH and rates of oxygen radical formation induced by chlordecone. 171 Apr 60

1. It has been established that chronic hyperammonaemia, whether caused by portacaval shunting or other means, leads to a variety of metabolic changes, including a depression in the cerebral metabolic rate of glucose (CMRGlc) increased permeability of the blood-brain barrier to neutral amino acids, and an increase in the brain content of aromatic amino acids. The preceding paper [Jessy, DeJoseph & Hawkins (1991) Biochem. J. 277, 693-696] showed that the depression in CMRGlc caused by hyperammonaemia correlated more closely with glutamine, a metabolite of ammonia, than with ammonia itself. This suggested that ammonia (NH3 and NH4+) was without effect. The present experiments address the question whether ammonia, in the absence of net glutamine synthesis, induces any of the metabolic symptoms of cerebral dysfunction associated with hyperammonaemia. 2. Small doses of methionine sulphoximine, an inhibitor of glutamine synthetase, were used to raise the plasma ammonia levels of normal rats without increasing the brain glutamine content. These hyperammonaemic rats, with plasma and brain ammonia levels equivalent to those known to depress brain function, behaved normally over 48 h. There was no depression of cerebral energy metabolism (i.e. the rate of glucose consumption). Contents of key intermediary metabolites and high-energy phosphates were normal. Neutral amino acid transport (tryptophan and leucine) and the brain contents of aromatic amino acids were unchanged. 3. The data suggest that ammonia is without effect at concentrations less than 1 mumol/ml if it is not converted into glutamine. The deleterious effect of chronic hyperammonaemia seems to begin with the synthesis of glutamine.
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PMID:Hyperammonaemia does not impair brain function in the absence of net glutamine synthesis. 187 6

To elucidate the mechanisms involved in the inhibition of synaptic transmission by ammonium ions, the effects of NH4Cl on glutamate release and on synaptic transmission from Schaffer collaterals to CA1 pyramidal cells were measured in fully submerged slices of rat hippocampus. The large, Ca(2+)-dependent release of glutamate evoked by electrical-field stimulation or by 56 mM K+ was not reduced by 5 mM NH4Cl. In contrast, 5 mM NH4Cl decreased the smaller, field stimulation-induced release of glutamate observed in the presence of low concentrations of Ca2+ (0.1 mM), as well as the spontaneous release of glutamate both in normal and low Ca2+. Unlike the Ca(2+)-dependent release of glutamate, synaptic transmission was reversibly depressed even by 1 mM NH4 Cl. Firing of CA1 pyramidal cells evoked by iontophoretically applied glutamate was significantly inhibited by 2 or 5 mM NH4Cl. This depression was increased in the presence of 25 microM bicuculline. Results suggest that ammonium ions do not depress the Ca(2+)-dependent release of glutamate originating from synaptic vesicles, which is involved in synaptic transmission. Rather, ammonium ions inhibit synaptic transmission by a postsynaptic action, a conclusion strengthened by the inhibitory effect of NH4Cl on glutamate-induced firing. However, NH4Cl may inhibit the formation of cytoplasmic glutamate, the source of spontaneous and Ca(2+)-independent release.
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PMID:Neurochemical and electrophysiological studies on the inhibitory effect of ammonium ions on synaptic transmission in slices of rat hippocampus: evidence for a postsynaptic action. 196 24

The crystal structure of a class A beta-lactamase from Staphylococcus aureus PC1 has been refined at 2.0 A resolution. The resulting crystallographic R-factor (R = sigma h parallel Fo[-]Fc parallel/sigma h[Fo], where [Fo] and [Fc] are the observed and calculated structure factor amplitudes, respectively), is 0.163 for the 17,547 reflections with I greater than or equal to 2 sigma (I) within the 8.0 A to 2.0 A resolution range. The molecule consists of two closely associated domains. One domain is formed by a five-stranded antiparallel beta-sheet with three helices packing against a face of the sheet. The second domain is formed mostly by helices that pack against the second face of the sheet. The active site is located in the interface between the two domains, and many of the residues that form it are conserved in all known sequences of class A beta-lactamases. Similar to the serine proteases, an oxyanion hole is implicated in catalysis. It is formed by two main-chain nitrogen atoms, that of the catalytic seryl residue, Ser70, and that of Gln237 on an edge beta-strand of the major beta-sheet. Ser70 is interacting with another conserved seryl residue, Ser130, located between the two ammonium groups of the functionally important lysine residues, Lys73 and Lys234. Such intricate interactions point to a possible catalytic role for this second seryl residue. Another key catalytic residue is Glu166. There are several unusual structural features associated with the active site. (1) A cis peptide bond has been identified between the catalytic Glu166 and Ile167. (2) Ala69 and Leu220 have strained phi, psi dihedral angles making close contacts that restrict the conformation of the active site beta-strand involved in the formation of the oxyanion hole. (3) A buried aspartate residue, the conserved Asp233, is located next to the active site Lys234. It is interacting with another buried aspartyl residue, Asp246. An internal solvent molecule is also involved, but the rest of its interactions with the protein indicate it is not a cation. (4) Another conserved aspartyl residue that is desolvated is Asp131, adjacent to Ser130. Its charge is stabilized by interactions with four main-chain nitrogen atoms. (5) An internal cavity underneath the active site depression is filled with six solvent molecules. This, and an adjacent cavity occupied by three solvent molecules partially separate the omega-loop associated with the active site from the rest of the protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Refined crystal structure of beta-lactamase from Staphylococcus aureus PC1 at 2.0 A resolution. 200 20

Excitatory postsynaptic potentials (termed U1 and U2) were extracellularly recorded from the frog optic tectum in vitro following electrical stimulation of the contralateral optic nerve. Gamma-Aminobutyric acid (GABA) and glycine elicited a large and sustained enhancement of these synaptic waves. In the presence of the Cl- transport inhibitor ammonium (NH+4) the effects of GABA or glycine were progressively reduced to about 50% of their initial action without changes in the control synaptic waves. In 50% Cl- media the depression of GABA and glycine responses by NH+4 was more intense. Other Cl- transport inhibitors such as bumetanide, piretanide and 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonate (SITS) were inactive against responses to GABA or glycine. Penicillin, a Cl- channel blocker, antagonized the action of GABA and glycine, while increasing the amplitude of the U2 waveform. The present results provide pharmacological evidence in support of the Cl- dependence of the unusual action of GABA or glycine in facilitating excitatory synaptic transmission in the optic tectum.
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PMID:The effect of GABA on the frog optic tectum is sensitive to ammonium and to penicillin. 216 48

The toxicity of Cu, Ni and Fe individually, as well as in combination (Cu + Ni, Cu + Fe, Ni + Fe), on growth-rate depression, uptake of NO3- and NH4+, photosynthesis, nitrate reductase and urease activity of Chlorella vulgaris has been studied. All the test metals when used individually showed pronounced toxicity on all the parameters studied. However, their interactive effect was mostly antagonistic except for Cu + Ni (synergism). Pre-addition of Fe offered more protection to the cells against copper and nickel toxicity. The data of statistical analysis reconfirmed that 14CO2 uptake is the most sensitive parameter (significant at P less than 0.005, both for time and treatment) than others in metal toxicity assessment. However, these results suggest further that exposure time and sequence of metal addition are very important in biomonitoring of heavy metal toxicity.
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PMID:Impact of bimetallic combinations of Cu, Ni and Fe on growth rate, uptake of nitrate and ammonium, 14CO2 fixation, nitrate reductase and urease activity of Chlorella vulgaris. 216 14

Results of ammonium convulsive therapy (ACT) in 203 patients with neurotic depressive states of various nosological origin are presented. In the total population subjected to 4-20 sessions of ACT, a full recovery or a good remission were attained in 89% of patients. The remission starts after 2 to 4 sessions with the improvement of basic mood and reducing of anxiety. Later continuous activation of the behavior may be seen. The best results were attained in patients with depressive, hypochondriac and neurasthenic neuroses, especially when astheno-, anxious-depressive or astheno-hypochondriac syndromes predominated. ACT is well tolerated by patients with no marked side effects. ACT can be recommended as a safe and effective treatment method in patients with moderate depression.
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PMID:[A reduced variant of convulsive therapy with ammonium chloride in patients with neurotic depression]. 216 34

Sodium dimercaptopropanesulphonate (DMPS) and sodium dimercaptosuccinate (DMS) were discovered to be effective antidotes for acute poisoning of insecticides SCD [sodium ammonium dimethyl-2-(propane-1,3-dithiosulfate) monohydrate], nereistoxin (4-N,N-dimethylamino-1,2-dithiolane) and cartap (dihydronereistoxin dicarbamate). In mice, DMPS (250 mg/kg) or DMS (1000 mg/kg) ip 20 min before SCD increased LD50 of ig SCD from 97 to 374 or 251 mg/kg, respectively. The prophylactic effect of DMPS was better than that of DMS. Administration of DMPS prior to cartap increased LD50 of ig cartap from 130 to 375 mg/kg. The therapeutic effect of DMPS was also demonstrated in SCD-poisoned conscious rabbits. DMPS 62.5 mg/kg or DMS 500 mg/kg iv completely antagonized the neuromuscular blockade and respiratory depression caused by SCD, nereistoxin and cartap in anesthetized rabbits. The antagonism of SCD-induced neuromuscular blockade by cysteine (400 mg/kg, iv) was less effective and of shorter duration than that by DMPS and DMS. Dimercaprol 50 mg/kg im showed little effect on SCD-induced paralysis. The antagonistic actions of sulfhydryl compounds on neuromuscular blockade induced by these insecticides probably belong to chemical antagonism.
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PMID:[Antidotal effects of sulfhydryl compounds on acute poisonings by sodium ammonium dimethyl-2-(propane-1,3-dithiosulfate) monohydrate, nereistoxin and cartap]. 217 10

In experiments with dialized neurons of L. stagnalis mollusc the recovery of Na-current (INa) after its depression by local anesthetic trimecaine and its quaternary derivative N-ethyltrimecaine (G-88) was studied. A full recovery of INa within tens of seconds after washing off trimecaine but not G-88 was observed. The half-time for vanishing of INa use-dependent depression by G-88 was 17 minutes, and there was no substantial vanishing of tonic INa block even after an hour of G-88 washing off. A hypothesis is advanced that the long recovery time of INa is one of the mechanisms providing long pharmacological action of quaternary antiarrhythmic and local anesthetic ammonium compounds.
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PMID:[Possible mechanism of long-term anti-arrhythmia and local anesthetic effect of quaternary ammonium compounds]. 244 64

The effects of sodium selenite on the neuromuscular junction of the phrenic nerve-diaphragm of the mouse were studied. Nerve-evoked twitches of the diaphragm of the mouse, the frequency of miniature endplate potentials, the quantal content of endplate potentials and the compound action potentials of the axon were measured. Sodium selenite induced a slight increase of the amplitude of the twitch, followed by twitch depression. The amplitude of the twitch, increased by selenite, became more prominent after the suppression of the twitch induced by cadmium ions, d-tubocurarine or magnesium ions. It appeared that the increased amplitude of twitch was due to the facilitation of transmitter release, since selenite significantly increased the frequency of miniature endplate potentials, and the amplitude and quantal content of endplate potentials; the amplitude and half decay time of miniature endplate potentials were unaffected. Twitch depression induced by selenite was enhanced by ammonium ions, high potassium and low magnesium and attenuated by high calcium. During the period of gradual depression of the twitch, selenite decreased the amplitude of compound action potentials of the phrenic nerve axon and caused the disappearance of endplate potentials. Ammonium ions enhanced the blockade of axonal conduction induced by selenite. Moreover, the depolarizing agents, ammonium and high potassium also induced an initial increase of twitch amplitude followed by depression of the twitch. These findings indicate that selenite probably alters the release of the transmitter by depolarizing the nerve membrane. The effects of selenite were antagonized by glutathione and cyanide, suggesting that the binding of selenite to sulfhydryl groups of the membrane was essential for inducing its pharmacological actions.
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PMID:Effects of sodium selenite on neuromuscular junction of the mouse phrenic nerve-diaphragm preparation. 247 66


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