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)

Administration of either Escherichia coli asparaginase or guinea pig serum to C3H/HE mice with the 6C3HED lymphosarcoma is followed by depression of glycine in the tumor. This decrease in cellular glycine concentration does not occur in a tumor resistant to asparaginase. The inhibition of the lymphosarcoma by asparaginase can be reversed by intraperitoneal injection of asparagine or glycine. This reversal appears to be specific because lysine, threonine, serine, and aspartic acid were ineffective. Loss of cellular glycine may be more important than loss of asparagine because of the requirement for glycine in purine synthesis.
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PMID:Glycine inhibition of asparaginase. 490 4

Five experiments were conducted using crystalline amino acid and semipurified diets containing adequate levels of all indispensable amino acids, vitamins, and minerals to study the effects of dispensable amino acids on growth and the incidence of leg abnormalities of male chicks. Purified diets containing 5% L-glutamic acid as the sole source of nonspecific nitrogen resulted in poor growth and feed efficiency, high mortality, and a high incidence of leg abnormalities with many severe cases of this condition. Increasing the dietary level of L-glutamic acid to 10% of the purified diet or supplementing the 5% L-glutamic acid diet with 2.40% glycine or 1.68% L-serine improved weight gain but did not eliminate the leg conditions. Higher L-serine (3.36%) resulted in a growth depression, indicating that this level was toxic to the birds. It was necessary to increase the dietary L-glutamic acid to 12.5% to reduce the incidence of leg problems to a minimum. Plasma dispensable amino acid levels (aspartic acid, glutamic acid, and alanine) paralleled the levels of L-glutamic acid in the diets fed to the chicks. Plasma serine and glycine levels were increased by adding either serine or glycine, but the magnitude of the increase of either amino acid was greatest with the addition of that amino acid to the diet. Plasma proline concentrations increased when chick diets were supplemented with high levels of glycine (2.4%), serine (3.36%), or glutamic acid (9.7%) in relation to those supplemented with only 5% L-glutamic acid. Feeding an intact protein (isolated soybean protein) diet did not alleviate leg disorders, although it did improve weight gain.
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PMID:Effects of a nonspecific nitrogen deficiency on growth rate and leg problems in chicks. 614 10

Lysophosphatidylserine is a specific inducer of histamine release in isolated mast cells. To determine whether a similar effect is manifest in vivo, the phospholipid was injected (1-5 mg/kg i.v.) into mice and rats. A dose-dependent rise in blood histamine was observed in both animals. The several-fold increase in blood histamine occurred in the first minutes and was followed by a slower decline toward normal values. A second dose of lysophosphatidylserine was without effect. Systemic manifestations (depression, hypothermia, hypotension) were associated with the increased blood histamine level. When the tissue histamine stores accessible to lysophosphatidylserine were previously decreased by repeated phospholipid injections, no systemic symptoms occurred. Mobilization of carbohydrate reserves was also manifest during the action of lysophosphatidylserine. Prior treatment with compound 48/80 induced sustained refractoriness to lysophosphatidylserine. Structure-activity relationship demonstrated that the property to induce histamine release was linked to the structure of serine head group. Thus, other natural phospholipids or lysophospholipids were inactive. It is concluded that in analogy with the effect seen in vitro lysophosphatidylserine produces in vivo release of mast cell histamine.
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PMID:Lysophosphatidylserine as histamine releaser in mice and rats. 620 97

Plasma amino acid abnormalities are frequently reported in alcoholics, with the most common abnormalities being those of depressed branched chain amino acids (BCAA) and increased aromatic amino acids. The depression in branched chain amino acids is due to multiple factors including portal-systemic shunting, hyperinsulinemia, hyperglucagonemia (all due to advanced liver disease) as well as dietary deficiency. alpha-Amino-n-butyric acid is a nonessential amino acid derived primarily from the catabolism of methionine, threonine, and serine. Increased levels due to chronic alcohol consumption may reflect altered glutathione metabolism and lipid peroxidation due to alcohol and may be used empirically as a biochemical marker of heavy drinking. The high levels of aromatic amino acids such as tyrosine and tryptophan as well as their breakdown products may be due to impaired hepatic metabolism and appear to play a role in the pathogenesis of hepatic encephalopathy. The effects of high levels of aromatic amino acids may be potentiated by depressed BCAA; these normally compete with each other for CNS transport. Alterations in these amino acids may have implications for nutritional requirements for amino acids in these patients as well as therapeutic approaches.
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PMID:Plasma amino acids in the alcoholic: nutritional aspects. 634 43

Experiments were conducted to determine the metabolic fate of threonine in chicks fed threonine-imbalanced diets. Threonine imbalance was produced by the addition of 3% serine to a threonine-limited diet, and prevented by the addition of 0.2% threonine to the diet. Serine decreased plasma and liver free threonine concentrations, and increased hepatic threonine dehydrogenase and threonine aldolase activities. All changes, including reduced food intake, appeared to occur within 1 day of feeding the imbalanced diet. Despite the decrease in free threonine concentrations and the increase in threonine aldolase and threonine dehydrogenase activities, net threonine catabolism was not markedly increased. This was evidenced by similar amounts of 14CO2 exhaled by chicks fed control and imbalanced diets containing L-[U-14C] threonine, and by similar growth of chicks that were forced-fed both diets to maintain equivalent food intake. It is possible that increases in threonine catabolism contribute to depressions of plasma and tissue threonine concentrations. However, the growth depression caused by serine-induced threonine imbalance is due to depressed food intake.
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PMID:Threonine metabolism of chicks fed threonine-imbalanced diets. 681 40

The chick's choline and methionine requirements are both increased by high dietary protein level. Studies were conducted to test the hypothesis that the chicks' need for preformed methyl groups is increased by high protein diets (not methionine or choline per se). Chicks fed 25% isolated soybean protein (ISP) diets responded to methionine supplementation (162 vs 110 g gained in 14 days) but not to choline (119 g vs. 110 g), while those fed 50% ISP responded to either methionine (174 g vs. 126 g) or choline (181 g vs. 126 g) supplementation. Further, neither cystine nor homocystine could replace methionine in improving the growth of chicks fed the high protein diet. In other experiments, L-methionine and betaine HCl were found to alleviate the growth depression caused by excessive levels of L-glutamic acid. Excessive levels of L-methionine had a protective effect against growth depression caused by L-glutamate and diammonium citrate, and conversely, supplementary L-serine and sodium formate were not protective against glutamic acid- or arginine-induced growth depression. The results are consistent with the hypothesis that the preformed methyl group requirement is increased by high levels of dietary protein and excessive nitrogen from a single amino acid.
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PMID:The effects of high dietary protein and nitrogen levels on the preformed methyl group requirement and methionine-induced growth depression in chicks. 726 36

Long-term potentiation (LTP) is a synaptic mechanism thought to be involved in learning and memory. Long-term depression (LTD), an activity-dependent decrease in synaptic efficacy, may be an equally important mechanism which permits neural networks to store information more effectively. One form of LTD that has been observed in the hippocampus requires activation of postsynaptic NMDA (N-methyl-D-aspartate) receptors, a change in postsynaptic calcium concentration, and activation of postsynaptic serine/threonine protein phosphatase 1 (PP1) or 2A (PP2A). The mechanism by which PP1 or PP2A is regulated by synaptic activity is unclear because these protein phosphatases are not directly influenced by calcium concentration. LTD induction may require activation of a more complex protein phosphatase cascade consisting of the Ca2+/calmodulin-dependent protein phosphatase, calcineurin, its phosphoprotein substrate, inhibitor-1, and PP1. We tested this hypothesis using calcineurin inhibitors as well as different forms of inhibitor-1 loaded into postsynaptic cells. Our results suggest a signalling pathway in which calcineurin dephosphorylates and inactivates inhibitor-1. This in turn increases PP1 activity and contributes to the generation of LTD.
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PMID:Involvement of a calcineurin/inhibitor-1 phosphatase cascade in hippocampal long-term depression. 751 79

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.
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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

1. The pharmacology of the metabotropic glutamate receptor (mGluR) that mediates synaptic depression at corticostriatal synapses was investigated with the use of field potential and whole cell patch-clamp recording from striatal slices and whole cell recordings from isolated striatal neurons. 2. The mGluR2,3-selective agonists (R,S)-4-carboxy-3-hydroxyphenylglycine (CHPG), (2S, 1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl) glycine (DCG-IV), and (2S, 3S, 4S)-alpha-(carboxycyclopropyl) glycine (L-CCG-I) inhibited the synaptically driven population spike (PS) evoked by afferent stimulation during field potential recording in striatal slices. These agonists also inhibited excitatory postsynaptic potentials (EPSPs) evoked by afferent stimulation during whole cell recordings. The metabotropic receptor antagonist R,S-alpha-methyl-4-carboxyphenylglycine (MCPG) blocked the synaptic depressant actions of DCG-IV and trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD). 3. The mGluR4,6,7-selective agonist L-serine-O-phosphate (L-SOP) did not alter corticostriatal synaptic transmission, but both this agonist and the mGluR4,6,7 agonist D,L-2-amino-4-phosphonobutyric acid (AP4) reduced the amplitude of the population EPSP and PS evoked in the dentate gyrus (DG) by stimulation of the lateral perforant path (LPP). These data are consistent with earlier observations that AP4 does not inhibit corticostriatal transmission, but produces presynaptic depression at LPP-DG synapses. 4. Application of mGluR agonists that inhibited transmission did not alter the input resistance or excitability of striatal neurons and did not inhibit responses evoked by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor activation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabotropic glutamate receptor-mediated presynaptic depression at corticostriatal synapses involves mGLuR2 or 3. 760 56

A cDNA encoding the human metabotropic glutamate receptor type 4 (hmGluR4) was isolated from human brain cDNA libraries by cross-hybridization with rat mGluR4 probes. The deduced amino acid sequence of human mGluR4 consists of 912 residues and shows a sequence identity of 96% to the amino acid sequence of rat mGluR4. Northern blot analyses indicate that hmGluR4 is strongly expressed in the cerebellum of the adult human brain but also at low levels in hippocampus, hypothalamus and thalamus. Stimulation of hmGluR4 with L-2-amino-4-phosphonobutyrate (L-AP4), L-serine-O-phosphate (L-SOP), L-glutamate or (1S,3R)-1-aminocyclo-pentane-1,3-dicarboxylic acid ((1S,3R)-ACPD) in stably transfected Chinese hamster ovary (CHO) cells depressed forskolin-induced cAMP accumulation, whereas quisqualate (0.5 mM) was ineffective. The rank order of agonist potencies is: L-AP4 > L-SOP > L-glutamate > (1S,3R)-ACPD >> quisqualate. (R,S)-alpha-methyl-4-carboxyphenylglycine (1 mM), a reported antagonist at some mGluR subtypes, did not reduce the depression of forskolin-induced cAMP accumulation by L-AP4.
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PMID:Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 4. 761 40


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