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)

In most cases, depression involves the interaction of biological and psychosocial factors. The impact of biological factors seems to be more prominent in major depressive syndrome, where typical symptoms and signs such as decrease in weight, changes in libido, dysmenorrhea, and sleeping disorders cannot be explained on psychodynamic grounds alone. Some of the symptoms and signs typical of patients suffering from depression reflect a primary disorder of biochemical and neurophysiological functions and are not commonly found in other forms of psychic disturbances. Studies related to monoamine (noradrenaline, serotonin or 5-HT, dopamine) metabolism have assumed a major role in biochemical research into depression; this research now also includes studies on other central neurotransmitters such as GABA and glutamic acid, and neuropeptides like somatostatin and corticotropin-releasing factor (CRF). Several theories have been suggested for the biochemical background of depression, and these hypotheses can now be tested using new and sophisticated research methods. Recent progress in understanding receptor structure and function and the regulation of neuroendocrine functions will substantially increase our knowledge of the biological deviations in depression and eventually lead to better drugs and treatment strategies. In the following, current perspectives on the biology of depressive disorders are introduced. It seems clear that susceptibility to depression is linked with deviations in presynaptic and postsynaptic neurotransmitter turnover and function. These, in turn, may lead to alterations in other regulatory mechanisms, such as the neuroendocrine and immune systems.
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PMID:Biological aspects of depression. 791 94

We studied changes in plasma levels of neuroexcitatory amino acids during and between migraine attacks in 16 patients with migraine without aura, 11 with aura and 21 controls. Glutamic acid levels between attacks were 1.027 +/- 0.60 and 0.890 +/- 0.41 mg/dl in migraine patients without and with aura, respectively; during attacks the levels were 0.535 +/- 0.23 and 0.601 +/- 0.20 for the same patients. The concentration of glutamic acid in the control group was 0.980 +/- 0.64 mg/dl. Aspartic acid levels between attacks in patients without and with aura were 0.179 +/- 0.04 and 0.167 +/- 0.03 mg/dl. Concentrations during attacks were 0.129 +/- 0.02 and 0.119 +/- 0.02 mg/dl for the same patients. Plasma levels of aspartic acid for controls were 0.146 +/- 0.03 mg/dl. We found no significant variations in neuroexcitatory amino acids between migraine attacks in patients with an without aura; changes took place only during attacks, possibly related to the mechanisms of the spreading depression process.
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PMID:[Changes in neuroexcitatory amino acids during and between migraine attacks]. 820 47

Deletion of the SLT2 gene of Saccharomyces cerevisiae, which codes for a homologue of MAP (mitogen-activated) protein kinases, causes an autolytic lethal phenotype in cells grown at 37 degrees C. The gene encodes domains characteristic of protein kinases, which include a lysine (at position 54) that lies 19 residues from a glycine-rich cluster, considered to be the putative ATP binding site. The ability of three mutant alleles of SLT2 generated by site-directed mutagenesis, namely E54 (glutamic acid), R54 (arginine) and F54 (phenylalanine), to complement slt2 mutants was tested. All three failed to complement the autolytic phenotype and were unable to restore growth and viability of cells. A strain obtained by transplacement of slt2-F54 also behaved as a thermosensitive autolytic mutant. By immunoprecipitation with polyclonal antibodies raised against Slt2 protein expressed in Escherichia coli, it was possible to confirm that alteration of the lysine-54 residue did not affect the stability of the protein, thus allowing us to conclude that activity of the Slt2 protein kinase is critically required for growth and morphogenesis of S. cerevisiae at 37 degrees C. A significant fraction of the mutant cell population lysed at 24 degrees C and the cells displayed a characteristic alteration of the surface consisting of a typical depression in an area of the cell wall. At 37 degrees C, the cell surface was clearly disorganized.
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PMID:Activity of the yeast MAP kinase homologue Slt2 is critically required for cell integrity at 37 degrees C. 823 2

In a chronic toxicity study in the rat, bidisomide administered as a dietary admixture produced a dose-related lowering of reticulocytes and leucocytes. Plasma alanine aminotransferase activity was increased at 300 mg/kg and decreased at 900 mg/kg. The potential mechanisms of these effects were investigated by comparing the responses in groups of male Sprague-Dawley rats receiving a control diet, or 300 or 1200 mg/kg/day bidisomide. Subsets of these groups were co-treated subcutaneously with folinic acid or with a vitamin B1, B6, B12 complex. Subsets of control and 300 mg/kg groups were maintained on a 20-25% feed restriction regimen for 3 months, to mimic the depression in body weight gain observed in animals receiving 1200 mg/kg. Body weight gains were significantly reduced at 1200 mg/kg and in all feed-restricted animals. Plasma and liver alanine aminotransferase (ALT) and plasma aspartate aminotransferase (AST) levels were also reduced at this dose level. At 300 mg/kg, plasma transaminases, glutamate dehydrogenase (GLDH) and sorbitol dehydrogenase (SDH) activities were increased. These changes were prevented in animals receiving folinic acid supplementation. Plasma glucose, triglycerides, and unsaturated and total iron binding capacities were decreased, while plasma iron levels tended to increase, mainly at the high dose. Vitamin supplementation prevented a decrease in reticulocyte counts at 300 mg/kg. Bidisomide increased urinary formimino-glutamic acid (FIGLU) excretion but did not affect methylmalonic acid (MMA) or taurine excretion. The effect on FIGLU at 1200 mg/kg was prevented by folinic acid co-treatment. Absolute liver weight was lowered at both dose levels and in feed-restricted animals. However, the relative liver weights were unaffected. Thymidine kinase and thymidylate synthase activity of the bone marrow cells were not altered by the bidisomide treatment. Except for the increase in plasma transaminase, GLDH and SDH levels at 300 mg/kg, changes in clinical chemistry parameters are considered to result mainly from nutritional restrictions. Changes in hematologic parameters appear to be related to the combination of decreased feed consumption (leukocytes) and decreased availability or utilization of folates (reticulocytes). This alteration, however, did not affect DNA synthesis in bone marrow. The prevention by folinic acid, but not by feed restriction, of the elevation of liver enzymes at 300 mg/kg is an intriguing, yet unexplained finding. There was no evidence that bidisomide affected B6 and B12 availability.
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PMID:Effect of folate supplementation on clinical chemistry and hematologic changes related to bidisomide administration in the rat. 858 20

Circulating phagocytic cells (hemocytes) of the snail Biomphalaria glabrata, intermediate host of the human blood fluke Schistosoma mansoni, were treated with the tetrapeptide, arg-gly-asp-ser (RGDS), an integrin-specific adhesion inhibitor, and assessed for their ability to adhere and spread on uncoated and snail plasma protein-coated glass slides. Although cells were capable of adherence, RGDS significantly inhibited the spreading ability of hemocytes in both a time and RGDS concentration-dependent fashion regardless of plasma protein coating. The inhibition of hemocyte spreading by RGDS was a specific response, since treatment of cells with a glutamic acid-substituted control peptide (RGES) did not exert the same inhibitory effect. A comparison of RGDS-responses between hemocytes of two strains of B. glabrata, one resistant (R; 13-16-R1 strain) and the other susceptible (S; NMRI strain) to infection by S. mansoni, revealed several snail strain-specific differences. At concentrations of 0.5 mM RGDS, R snail hemocyte spreading was unaffected, whereas a significant depression of spreading was seen in cells of the S snail. Moreover, we observed that R strain hemocytes spread more rapidly on homologous plasma-coated surfaces than the S snail strain following peptide pretreatment and removal. These data suggest that hemocytes from S and R snails may differ either in the number of RGDS-binding receptors or in their affinity for the RGDS peptide. In order to identify the type(s) of integrin-like RGD-binding receptors that may be present on the surface of snail immunocytes, washed hemocytes were placed on various mammalian extracellular matrix proteins and evaluated for their spreading function in the presence of specific or non-specific peptides. Hemocyte aggregation or clumping was observed on all test protein substrates, and this aggregation behavior was specifically inhibited by RGDS. Thus, RGD-binding receptors appear to play a critical role in cellular motility on matrix-coated surfaces and/or cell-cell binding. Our data provide functional evidence for an integrin-like receptor on circulating phagocytes of snails, and for an RGD-binding mechanism involved in cell-substrate interactions.
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PMID:Integrin-like RGD-dependent binding mechanism involved in the spreading response of circulating molluscan phagocytes. 961 82

Synaptic activation of metabotropic glutamate receptors (mGluRs) in the locus coeruleus (LC) was investigated in adult rat brain slice preparations. Evoked excitatory postsynaptic potentials (EPSPs) resulting from stimulation of LC afferents were measured with current clamp from intracellularly recorded LC neurons. In this preparation, mGluR agonists (+/-)-1-aminocyclopentane-trans-1, 3-dicarboxylic acid (t-ACPD) and L(+)-2-amino-4-phosphonobutyric acid (L-AP4) activate distinct presynaptic mGluRs, resulting in an inhibition of EPSPs. When two stimuli were applied to afferents at intervals >200 ms, the amplitude of the second [test (T)] EPSP was identical in amplitude to the first [control(C)]. However, when a stimulation volley was delivered before T, the amplitude of the latter EPSP was consistently smaller than C. The activity-dependent depression (ADD) was dependent on the frequency and duration of the train and the interval between the train and T. ADD was potentiated in the presence of an excitatory amino acid (EAA) uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (t-PDC, 100 microM), changing the T/C ratio from 0.84 +/- 0.05 (mean +/- SE) in control to 0.69 +/- 0.04 in t-PDC (n = 9). In the presence of t-PDC, the depolarizing response of LC neurons to focally applied glutamate was also increased. Together, these results suggest that accumulation of EAA after synaptic stimulation may be responsible for ADD. To test if ADD is a result of the activation of presynaptic mGluRs, the effect of selective mGluR antagonists on ADD was assessed. In the presence of t-PDC, bath applied (S)-amino-2-methyl-4-phosphonobutanoic acid (MAP4, 500 microM), a mGluR group III antagonist, significantly reversed the decrease in T/C ratio after a train stimulation [from 0.66 +/- 0.04 to 0.81 +/- 0.02 (mean +/- SE), n = 5]. The T/C ratio in the presence of MAP4 was not different from that measured in the absence of a stimulation volley. Conversely, ethyl glutamic acid (EGLU, 500 microM), a mGluR group II antagonist, failed to alter the T/C ratio. Together, these results suggest that, in LC, group III presynaptic mGluR activation provides a feedback mechanism by which excitatory synaptic transmission can be negatively modulated during high-frequency synaptic activity. Furthermore, this study provides functional differentiation between presynaptic groups II and III mGluR in LC and suggests that the group II mGluR may be involved in functions distinct from those of group III mGluRs.
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PMID:Activity-dependent activation of presynaptic metabotropic glutamate receptors in locus coeruleus. 1071 44

Glutamic acid is the major excitatory neurotransmitter in the mammalian central nervous system (CNS). Specific receptors bind glutamate and some of these when activated open an integral ion channel and are thus known as ionotropic receptors. Within the ionotropic family of glutamate receptors, three major subtypes have been identified using classical specific agonist activation, selective competitive antagonists together with their structural heterogeneity. These receptors have thus been named N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainate receptors. The NMDA receptor has sites in addition to its agonist-binding site and these seem to either positively or negatively modulate the agonist effect. The NMDA receptor also is unique in that another amino acid, glycine, acts as a co-agonist with glutamate. Changes in glutamate transmission have been associated with a number of CNS pathologies; these include, acute stroke, chronic neurodegeneration, chronic pain, depression, drug dependency, epilepsy, Parkinson's Disease and schizophrenia.
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PMID:Excitatory amino acid agonists and antagonists: pharmacology and therapeutic applications. 1081 62

Isolated porcine coronary arteries (PCA) contracted by depolarization with high K0 or by histamine (10 microM) were relaxed concentration-dependently by glutamic acid, aspartic acid, N-methyl-D-aspartate (NMDA) and, gamma-aminobutyric acid (GABA). In the PCA preparations contracted by high K0 or histamine the effects were monophasic, but the histamine-induced effects were more sustained and of larger amplitude. The ED50 values of cumulative concentration-response (CCR) curves obtained for the relaxation induced by L-glutamate in histamine-stimulated PCA preparations were shifted from 0.8 mM to 0.25 microM in presence of 1 mM glycine, a co-agonist required for the activation of NMDA receptors. The relaxations resulting from low-affinity binding of L-glutamic were dependent on Ca0 as evidenced by the shift of CCR curves to the right in the presence of 5-100 mM K0. In contrast, CCR curves obtained for contractions induced by NaF (1.5-12 mM), were significantly shifted to the left (from 6.3 to 3.1 mM). A depression of the maximum effect observed at higher F- concentrations was reversed by addition of 5 mM Mg0. Data show that glutamate induces a vasorelaxation that may be associated with symptoms seen in Chinese restaurant syndrome.
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PMID:Vasorelaxation induced by L-glutamate in porcine coronary arteries. 1133 34

The purpose of this study was to characterize further the effects of loads of protein versus carbohydrate on subsequent food intake in rats. We used an intraoral cannula to deliver isoenergetic isovolumic loads, in a tightly controlled time frame allowing for both metabolic responses and orosensory components of the load. Our results showed that the gluten load (GLT-100%) induced a greater depression in food intake than an isocaloric wheat starch load (GLT-0%). The types of protein used in the load (total milk protein vs. GLT) did not seem to influence their appetite-suppressive effect. There was a dose-dependent effect of the satiating effects of the protein loads, the GLT-100% load being more effective than either the GLT-35% or GLT-50% loads. Pattern analysis of the meal following the load suggested that animals were more satiated by protein, at least when loads contained 35% or 50% of protein, than by carbohydrate. At least 1 day was necessary before we saw a significant decrease in the energy intake following the protein loads. Thus, the animals had to learn the postingestive effects of the loads before the response stabilized. Taken together, the present results confirm that protein has a greater satiating effect than carbohydrate and extend these results by revealing that the larger the proportion of protein in the food, the larger the satiating effect, and that the quality of protein does not seem to play a significant role.
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PMID:Protein is more potent than carbohydrate for reducing appetite in rats. 1206 22

Glutamate produces a hyperpolarizing postsynaptic potential in ON bipolar cells by binding to the metabotropic receptor mGluR6 and subsequently closing a cation-selective channel. It has been proposed that Ca(2+) influx through the cation channel triggers a depression of the synaptic potential. Here we report that this Ca(2+)-mediated depression requires activation of calcineurin, a Ca(2+)/calmodulin-regulated phosphatase. We measured glutamate-evoked currents (I(glu)) with whole cell recordings of ON bipolar cells in light-adapted retinal slices. Depression of I(glu) by Ca(2+) was prevented by inhibitors of calcineurin or by tightly buffering Ca(2+) with bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA). However, when cells were dialyzed with BAPTA and a Ca(2+)-independent form of calcineurin (CaN420), depression of I(glu) was restored. Similarly, CaN420 induced depression of I(glu) during continuous glutamate application, a protocol that ordinarily prevents depression. Analysis of changes in the amplitude of the cation-selective current (I(cat)) of cells that were dialyzed with high Ca(2+) (1 microM), or with BAPTA and CaN420, indicates that Ca(2+) depresses I(glu) by reducing I(cat) and that calcineurin acts via the same mechanism. Ca(2+)-mediated depression of I(glu) was not found to involve CaMKII, as inhibitors of CaMKII did not prevent this depression nor did they affect the sensitivity of the response to small changes in the concentration of mGluR6 agonist. Our data suggest that Ca(2+) and calcineurin may play an adaptive role at the synapse between photoreceptor and ON bipolar cells, closing postsynaptic cation channels that are opened by a drop in synaptic glutamate levels during prolonged photoreceptor illumination.
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PMID:Regulation of the retinal bipolar cell mGluR6 pathway by calcineurin. 1220 31


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