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)

Monoamine oxidase (MAO) is an enzyme that oxidizes various physiologically and pathologically important monoamine neurotransmitters and hormones such as dopamine, noradrenaline, adrenaline, and serotonin. Two types of MAO, i.e. type A (MAO-A) and type B (MAO-B), were first discovered pharmacologically. MAO-A is inhibited by clorgyline; and MAO-B, by deprenyl. cDNAs MAO-A and MAO-B were cloned and their structures determined. MAO-A and MAO-B are made of similar but different polypeptides and encoded by different nuclear genes located on the X chromosome (Xp11.23). MAO-A and MAO-B genes consist of 15 exons with identical intron-exon organization, suggesting that they were derived from a common ancestral gene. Both enzymes require a flavin cofactor, flavin adenine dinucleotide (FAD), which binds to the cysteine residue of a pentapeptide sequence (Ser-Gly-Gly-Cys-Tyr). Both enzymes exist on the outer membrane of mitochondria of various types of cells in various tissues including the brain. In humans, MAO-A is abundant in the brain and liver, whereas the liver, lungs and intestine are rich in MAO-B. MAO-A oxidizes noradrenaline and serotonin; and MAO-B, mainly beta-phenylethylamine. In the human brain, MAO-A exists in catecholaminergic neurons, but MAO-B is found in serotonergic neurons and glial cells. MAO-A knockout mice exhibit increased serotonin levels and aggressive behavior, whereas MAO-B knockout mice show little behavioral change. The gene knockout mice of MAO-A or MAO-B, together with the observation that some humans lack MAO-A, MAO-B, or both have contributed to our understanding of the function of MAO-A and MAO-B in health and disease. MAO-A and MAO-B may be closely related to various neuropsychiatric disorders such as depression and Parkinson's disease, and inhibitors of them are the subject of drug development for such diseases.
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PMID:Progress in monoamine oxidase (MAO) research in relation to genetic engineering. 1469 76

We investigated the effects of a 5-hydroxytryptamine (5-HT) 1A receptor gene polymorphism on the clinical response to fluvoxamine (FLV) in 65 depressed outpatients who gave written consent to participate in the study. Patients visited every 2 weeks after the first examination until the week 12 end point and were evaluated by the 17-item Hamilton Rating Scale for Depression (HAM-D-17) at each visit. FLV dose was changed in response to their clinical symptoms. The Gly272Asp polymorphism of the 5-HT1A receptor gene was identified by a PCR method. The subjects with the Asp allele had a significantly higher % reduction in the HAM-D-17 score than those with the Gly/Gly genotype at week 2 (P=0.009), week 6 (P=0.036), and week 12 (P=0.031). There was a significant difference in the genotype distribution between the responders and nonresponders. These results suggest that the Gly272Asp polymorphism of the 5-HT1A receptor gene may predict the response to FLV.
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PMID:The effects of a 5-hydroxytryptamine 1A receptor gene polymorphism on the clinical response to fluvoxamine in depressed patients. 1514 1

Glutamate is the primary excitatory neurotransmitter in the mammalian brain. Glutamatergic neurotransmission may be modulated at multiple levels, only a minority of which are currently being exploited for pharmaceutical development. Ionotropic receptors for glutamate are divided into N-methyl-D-aspartate receptor (NMDAR) and AMPA receptor subtypes. NMDAR have been implicated in the pathophysiology of schizophrenia. The glycine modulatory site of the NMDAR is currently a favored therapeutic target, with several modulatory agents currently undergoing clinical development. Of these, the full agonists glycine and D-serine have both shown to induce significant, large effect size reductions in persistent negative and cognitive symptoms when added to traditional or newer atypical antipsychotics in double-blind, placebo-controlled clinical studies. Glycine (GLYT1) and small neutral amino-acid (SNAT) transporters, which regulate glycine levels, represent additional targets for drug development, and may represent a site of action of clozapine. Brain transporters for D-serine have recently been described. Metabotropic glutamate receptors are positively (Group I) or negatively (Groups II and III) coupled to glutamatergic neurotransmission. Metabotropic modulators are currently under preclinical development for neuropsychiatric conditions, including schizophrenia, depression and anxiety disorders. Other conditions for which glutamate modulators may prove effective include stroke, epilepsy, Alzheimer disease and PTSD.
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PMID:Glutamate as a therapeutic target in psychiatric disorders. 1527 97

Neonatal hypophysectomy in chicken, as well as that in old hen has been established to entail in 1,5 months after surgery cellular and humoral immunity disturbances, pronounced hypercoagulation and fibrinolysis depression. Administration of Epitalon (Ala-Glu-Asp-Gly) to a large extent eliminates revealed shifts. This effect appeared to be stronger in neonatally hypophysectomized chicken than in old hens.
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PMID:[Effect of epitalon on the immunity and hemostasis in hypophysectomized chicken and old hens]. 1549 Jul 30

The nucleus tractus solitarius (NTS) receives dense terminations from cranial visceral afferents, including those from the gastrointestinal (GI) system. Although the NTS integrates peripheral satiety signals and relays this signal to central feeding centers, little is known about which NTS neurons are involved or what mechanisms are responsible. Proopiomelanocortin (POMC) neurons are good candidates for GI integration, because disruption of the POMC gene leads to severe obesity and hyperphagia. Here, we used POMC-enhanced green fluorescent protein (EGFP) transgenic mice to identify NTS POMC neurons. Intraperitoneal administration of cholecystokinin (CCK) induced c-fos gene expression in NTS POMC-EGFP neurons, suggesting that they are activated by afferents stimulated by the satiety hormone. We tested the synaptic relationship of these neurons to visceral afferents and their modulation by CCK and opioids using patch recordings in horizontal brain slices. Electrical activation of the solitary tract (ST) evoked EPSCs in NTS POMC-EGFP neurons. The invariant latencies, low failure rates, and substantial paired-pulse depression of the ST-evoked EPSCs indicate that NTS POMC-EGFP neurons are second-order neurons directly contacted by afferent terminals. The EPSCs were blocked by the glutamate antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline. CCK increased the amplitude of the ST-stimulated EPSCs and the frequency of miniature EPSCs, effects attenuated by the CCK1 receptor antagonist lorglumide. In contrast, the orexigenic opioid agonists [D-Ala(2), N-Me-Phe(4), Gly-ol(5)]-enkephalin and met-enkephalin inhibited both ST-stimulated EPSCs and the frequency of miniature EPSCs. These findings identify a potential satiety pathway in which visceral afferents directly activate NTS POMC-EGFP neurons with excitatory inputs that are appropriately modulated by appetite regulators.
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PMID:Proopiomelanocortin neurons in nucleus tractus solitarius are activated by visceral afferents: regulation by cholecystokinin and opioids. 1581 88

Glycyl-glutamine (Gly-Gln; beta-endorphin(30-31)) is an endogenous dipeptide synthesized from beta-endorphin(1-31). Previous investigations have shown that Gly-Gln inhibits the cardiovascular and respiratory depression caused by morphine and beta-endorphin(1-31), but it does not interfere with opioid analgesia. In this study, we tested whether Gly-Gln administration would influence morphine-induced conditioned place preference, tolerance, dependence, or withdrawal. For place preference experiments, rats were conditioned with morphine sulfate (2.5 mg/kg i.p.) or saline on alternate days for 6 days and tested on day 7. Glycyl-glutamine (1-100 nmol i.c.v.) pretreatment inhibited acquisition of a conditioned place preference to morphine significantly. Glycyl-glutamine (100 nmol i.c.v.) also blocked expression of a pre-established morphine place preference, but it did not interfere with acquisition of a conditioned place preference to palatable food, and it did not produce place preference or aversion when given alone to morphine-naive animals. To induce antinociceptive tolerance, rats were treated with morphine (10 mg/kg i.p.) twice daily for 7 days, and morphine antinociception was evaluated with the tail-flick test. Glycyl-glutamine (100 nmol i.c.v.) pretreatment delayed the onset of morphine tolerance significantly and partially reversed pre-established tolerance. Morphine dependence and withdrawal were assessed by measuring naloxone-precipitated withdrawal symptoms. Glycyl-glutamine inhibited the development of morphine dependence when given to rats twice daily immediately before they received morphine (10 mg/kg i.p.) and suppressed withdrawal symptoms of rats with subcutaneously implanted morphine pellets when administered 5 min before withdrawal was induced with naloxone. Glycyl-glutamine thus attenuates morphine-induced conditioned place preference, tolerance, dependence, and withdrawal without compromising morphine analgesia.
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PMID:Glycyl-glutamine, an endogenous beta-endorphin-derived peptide, inhibits morphine-induced conditioned place preference, tolerance, dependence, and withdrawal. 1607 99

We have previously reported that the Ser9Gly dopamine D3 receptor (DRD3) polymorphism was associated with increased rates of obsessive-compulsive personality disorder (OCPD) symptomology. We tested the replicability of this association within a further two independent groups of individuals with a history of depression, from a clinical sample (n = 149) and a family study (n = 213). The data from the replication samples and the original sample, within which the association was found, were compiled within a meta-analysis. Although the independent samples did not replicate the original finding, the meta-analysis elucidated significant evidence supporting the association. An individual with Gly/Gly genotype is 2.4 (P = 0.017) times more likely to be diagnosed with OCPD. Male gender was also found to be a significant predictor of OCPD diagnosis (OR = 2.82, P = 0.001). An exploration of an association of DRD3 with Axis I anxiety disorder diagnoses and Temperament and Character Inventory (TCI) traits, in particular persistence, revealed no support for an association. We conclude that DRD3 may contribute to the development of OCPD.
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PMID:Preliminary evidence for an association between a dopamine D3 receptor gene variant and obsessive-compulsive personality disorder in patients with major depression. 1658 7

Soybean plants, Glycine max (L.) Merrill, in standard solution received 2.5 mum ferric ethylenediamine di(o-hydroxyphenylacetate (FeEDDHA) and 0 to 128 mum phosphorus. Their stem exudates contained: 32 to 52 mum Fe, 120 to 5000 mum P, and 120 to 165 mum citrate. Electrophoresis of exudates with high P caused Fe trailing that precluded identification of any major form of Fe. Exudate with low P gave an anodic band of Fe citrate as the major Fe compound. Phosphate added to exudate in vitro depressed the Fe citrate peak and cause Fe trailing. EDDHA added to exudate in vitro pulled Fe from Fe citrate; citrate then migrated as a slower form and Fe migrated as FeEDDHA. A modified preculture system, involving 2-day renewals of 0.2 mum FeEDDHA with 3.2, 9.6, or 16 mum P and low levels of other ions, controlled pH depression and produced considerable change in citrate and P levels. The exudates contained: 45 to 57 mum Fe, 200 to 925 mum P, and 340 to 1025 mum citrate. The high citrate was from plants grown with low P. The major form of Fe in the exudates was Fe citrate. This is probably the form translocated in the plants.
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PMID:Translocation of iron citrate and phosphorus in xylem exudate of soybean. 1665 13

Nodulated soybean plants (Glycine max [L.] Merr) were grown in sand culture without combined N or with a continuous supply of nitrate in nutrient solution. Moderate nitrate concentration (30 milligrams N per liter) had little effect on nodule weight/plant while high nitrate concentration (100 milligrams N per liter) depressed nodule weight/plant by 70 to 80% with harvests 30 to 60 days after planting and initiation of nitrate treatments.The effect of nitrate supply on ammonium, amino, and ureide nitrogen concentrations in nodules was small and inconsistent. In contrast, nitrate and nitrite concentrations in nodules were directly proportional to nitrate supply and inversely proportional to nodule weight/plant. Correlations between nitrate or nitrite concentration in nodules and nodule weight/plant were highly significant.Cytosol from soybean nodules was found to contain NADH-dependent nitrate reductase activity (typical activity was 0.1 micromole per milligram protein x hour). A Rhizobium japonicum mutant (derived from strain 61A76) lacking nitrate reductase was employed to show that the cytosol enzyme activity is of host origin. Growth of nodules formed by the mutant lacking nitrate reductase was inhibited by nitrate. These nodules did contain nitrite although concentrations of nitrite (about 0.3 microgram N per gram fresh weight) were low relative to nitrite concentrations (about 1.5 microgram N per gram fresh weight) in nodules formed by R. japonicum strain 61A76. The overall results support the idea that the depression of legume nodule growth by nitrate is directly related to the metabolism of nitrate in nodules.
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PMID:Synthesis and accumulation of nitrite in soybean nodules supplied with nitrate. 1666 17

Cotyledons of light-grown soybean (Glycine max L. var Wayne) seedlings were used as a model system to study the possibility that aging requires qualitative changes in protein synthesis. Cotyledons reached a final stage of senescence and then abscised about 22 days after imbibition. Cotyledon senescence was reversed at 20 days after germination by epicotyl removal. Thereafter, the cotyledons regained much of the chlorophyll, RNA, protein, and polyribosomes lost during aging.Total poly(A)mRNA was extracted from 4-, 12-, 20-day-old, and rejuvenated cotyledons and translated in a wheat germ system. Comparison of translation products on two-dimensional O'Farrell gels showed that many translation products increased in quantity during aging, while roughly half as many decreased. Rejuvenation returned the translation products to approximately 4-day-old levels in roughly half of those products which were diminished with age. Conversely, almost one-third of the products which had increased with age decreased with rejuvenation. None of the translation products were totally lost nor were newly synthesized products detected during aging. Therefore, aging in this system probably does not involve complete gene repression or depression. The observation that epicotyl removal causes a reversal in the levels of various proteins synthesized in vitro was corroborated by similar observations following in vivo labeling of cotyledon sections and analysis by SDS-polyacrylamide gel electrophoresis and fluorography. Densitometric scans of fluorograms revealed a gradual shift in profiles of both in vitro and in vivo translation products during aging. Rejuvenated cotyledon proteins had a profile resembling that of 4-day-old cotyledons. The overall level of [(35)S]methionine incorporation into protein in vivo declined gradually during aging but was restored to 4-day-old levels within 2 days after epicotyl removal.
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PMID:Quantitative changes in in vitro and in vivo protein synthesis in aging and rejuvenated soybean cotyledons. 1666 20


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