Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

A 1-month-old Jersey calf died of oxalate nephropathy. The calf had access to antifreeze (ethylene glycol) 3 days prior to death. Since ethylene glycol toxicosis had not been reported in cattle, the effects or oral administration of ethylene glycol were studied in 7 calves and 3 cows. The toxic dose ranged from 2 to 10 ml of ethylene glycol per kg of body weight. Clinical signs were increased respiration, staggering gait, paraparesis, depression and later, recumbency and death. Hemoglobinuria and epistaxis were seen at doses of 10mg/kg of body weight. Azotemia, hypocalcemia and neutrophilia were constant findings whereas acidosis, plasma hyperosmolality and hemolytic anemia were seen in the animals receiving the higher doses. A diagnosis of ethylene glycol toxicosis must be based upon a history of ingestion and the presence of calcium oxalate crystals in body tissues (especially the kidney and brain).
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PMID:Ethylene glycol toxicosis in cattle. 47 24

The recent discovery and characterization of three new 5-HT1 receptor clones and the pharmacological characterization of one orphan receptor (dog RDC4) has revealed a surprising complexity within the 5-HT1D receptor subfamily. This receptor subfamily, which is believed to be the target of the anti-migraine drug sumatriptan and may regulate feeding behavior, anxiety, depression, cardiac function and movement, can now be approached on a molecular level. These cloning discoveries have also taught us an important general lesson about the molecular pharmacology of G protein-coupled receptor genes: species homologues of a gene (the equivalent gene in different species) may be highly homologous in amino acid sequence yet display very different pharmacological properties. Conversely, two different genes in the same species (intraspecies subtypes) that display only moderate degrees of transmembrane amino acid homology can display nearly indistinguishable pharmacological properties. In discussing the implications of these findings for both 5-HT receptors and G protein-linked receptors in general, Paul Hartig, Theresa Branchek and Richard Weinshank approach the question: why have so many receptor subtypes been preserved in the genome? In addition, controversy has been raging for several years over the classification of 5-HT1B receptors (found only in rat brain) and 5-HT1D receptors. Were they different subtypes or simply species homologues of the same receptor? Recent cloning studies have apparently complicated this issue, but the answer to the question is, in fact, becoming clearer.
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PMID:A subfamily of 5-HT1D receptor genes. 158 9

Because diazepam binding inhibitor (DBI) and its processing products coexist with gamma-aminobutyric acid (GABA) in several axon terminals, DBI immunoreactivity was measured in the cerebrospinal fluid (CSF) of individuals suffering from various neuropsychiatric disorders, that are believe to be associated with abnormalities of GABAergic transmission. Increased amounts of DBI-like immunoreactivity were found in the CSF of patients suffering from severe depression with a severe anxiety component (Barbaccia, Costa, Ferrero, Guidotti, Roy, Sunderland, Pickar, Paul and Goodwin, 1986). Moreover, the amount of DBI and its processing products was found to be increased in the CSF of patients with hepatic encephalopathy (HE) (Rothstein, McKhann, Guarneri, Barbaccia, Guidotti and Costa, 1989; Guarneri, Berkovich, Guidotti and Costa, 1990). The clinical rating of HE correlated with the extent of the increase in DBI in CSF. Other lines of research suggest that DBI and DBI processing products may be important factors in behavioral adaptation to stress, acting via benzodiazepine (BZD) binding sites, located on mitochondria. DBI and its processing products, ODN and TTN, are present in high concentrations in the hypothalamus and in the amygdala, two areas of the brain that are important in regulating behavioral patterns associated with conflict situations, anxiety and stress. In CSF, the content of DBI changes in association with corticotropin releasing factor (CRF) (Roy, Pickar, Gold, Barbaccia, Guidotti, Costa and Linnoila, 1989). Finally DBI is preferentially concentrated in steroidogenic tissues and cells (adrenal cortical cells, Leydig cells of the testes and glial cells of the brain).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of DBI in brain and its posttranslational processing products in normal and abnormal behavior. 166 69

For a range of rat tissue extracts, the concentrations of total folates and of short-chain pteroylpolyglutamates were assayed by Lactobacillus casei with and without conjugase treatment, respectively, and the concentration and chain length of H4PteGlnn and 5,10-CH2-H4PteGlnn together were assayed after binding to thymidylate synthase and tritiated fluorodeoxyuridylate. For rats fed a nonpurified diet and consuming 26 micrograms of folic acid daily, the respective concentrations of these total folates, short-chain folates and thymidylate synthase bindable folates were, in nmol/g, 10.2, 2.5 and 3.5 in liver, 3.9, 1.8 and 2.0 in kidney, 4.2, 1.2 and 1.0 in bone marrow, 2.3, 0.6 and 0.2 in adrenal, 2.1, 0.3 and 0.5 in spleen, 2.1, 0.9 and 0.8 in jejunal smooth muscle, 1.2, 0.9 and 0.2 in jejunal mucosa, 1.0, 0.3 and 0.6 in testis, 0.7, 0.1 and 0.2 in heart, 0.3, 0.1 and 0.1 in skeletal muscle, 0.5, 0.1 and 0.3 in brain and 0.7, 0.002 and 0 in erythrocytes. The predominant pteroylpolyglutamate chain length was 6 residues in all tissues except kidney, jejunal mucosa, skeletal muscle and brain, in which the value was 5 residues. A folate-deficient diet (30 ng/d) fed for 3 wk resulted in a depression in the total folate concentration of all tissues (except brain); the depression was generally greater for short-chain than for long-chain folates and was accompanied by a lengthening of the pteroylpolyglutamate chain. Opposite results followed folate excess of 4 to 5.4 mg/d. The fractional change in the folate concentration of the individual tissues, following perturbation of dietary folate, did not vary greatly among tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of pteroylpolyglutamate concentration and length in response to altered folate nutrition in a comprehensive range of rat tissues. 223 Oct 31

Cultured NCB-20 hybrid cells express adenylate cyclase-coupled receptors for 5-hydroxytryptamine (5-HT) that correspond biochemically and pharmacologically to 5-HT1 receptors in rodent brain membrane preparations, apart from a much-reduced affinity for 5-HT (160 nM compared to less than 5 nM in brain). Since NCB-20 cells also differ from rodent brain both qualitatively and quantitatively in their ganglioside composition, the effects of exogenously added gangliosides on the affinity of the 5-HT1 receptor for 5-HT were tested. Both GM1 ganglioside (the cholera toxin receptor) and tetrasialoganglioside GQ1b produced a 10-fold increase in receptor affinity for [3H]5-HT, measured by binding studies. All gangliosides, at submicromolar concentrations, resulted in significantly reduced EC50 values for 5-HT-mediated elevation of intracellular cyclic AMP levels. GQ1b had the capacity to most dramatically enhance the potency of 5-HT in mediating increases in cyclic AMP levels. Gangliosides had no effect on the potency of DADLE or 3,4-dihydroxyphenylethylamine (dopamine)-mediated depression of cyclic AMP levels, suggesting some specificity for 5-HT. Our data are interpreted as implying a specific role for polysialogangliosides in modulating the affinity of the 5-HT1 receptor and the coupling of the 5-HT1 receptor-guanine nucleotide binding protein adenylate cyclase complex.
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PMID:Possible role of gangliosides in regulating an adenylate cyclase-linked 5-hydroxytryptamine (5-HT1) receptor. 299 94

Two inbred mouse strains, SWR and CBA, differed significantly in their susceptibility to acute dose dependent theophylline- and caffeine-induced stimulation of locomotor activity. The efficacy of both methylxanthines was reduced in the SWR strain compared to the CBA strain. When brain levels of theophylline were determined at a dose (32 mg/kg IP) which gave maximal behavioral separation of the two strains, no significant differences were found between them (SWR levels 12.5 +/- 1.9, CBA levels 14.3 +/- 1.7 micrograms/g wet weight brain). The dose dependent ability of several adenosine agonists (N6-cyclohexyladenosine, (-)-N6-phenylisopropyladenosine, 5'-N-ethylcarboxamidoadenosine) to depress locomotor activity was investigated. SWR mice were found to be significantly more sensitive to NECA-induced depression of locomotor activity and the NECA-induced hypothermia than were CBA mice (respective ED50 values for inhibition of activity, 11.6 and 30.5 nmoles/kg IP). No differences were found in brain [3H]-NECA levels at doses which produced marked differences in behavioral effects between the two strains. The differences in adenosine agonist sensitivity between the strains were both agonist- and behavior-specific. These data indicate that an inherited alteration in behavioral responsiveness to methylxanthine administration can be inversely associated with inherent alterations in susceptibility to the action of specific adenosine analogs. An adenosine A-2 receptor sub-class may be involved in these changes in in vivo pharmacological susceptibility to the action of both methylxanthines and adenosine agonists on locomotor activity.
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PMID:Inherent hyporesponsiveness to methylxanthine-induced behavioral changes associated with supersensitivity to 5'-N-ethylcarboxamidoadenosine (NECA). 380 30

Non-Darwinian views of evolution of nervous systems (e.g., Jacksonian evolution) conceive the present structure of the human brain as composed of a series of additive layers representing successive phylogenetic stages in evolution, layers which remain static after their emergence. In contrast to this view, recent allometric studies clearly show that limbic structures scale with the growth of the human brain (i.e., they do not remain stable but reach the size expected for the brain of a primate with the weight of a human brain). Data also show that limbic structures are significantly involved in cognitive functions such as memory and attention. Hence overlap of lesions in similar brain loci, especially in limbic regions, in both manic-depression and schizophrenia should come as no surprise. In the psychobiological sphere, the need for cognitive perceptual evaluation of the external world and internal state for emotional experience, further to the necessary visceral arousal, leads to a breakdown of the platonic, essentialist position, emotion vs. cognition at the psychological level, a problematic issue for the Kraepelinean view. Neural networks operation depend upon multiple nonlinear processes at the cellular, synaptic and network levels. Afferent input may serve not only to activate, but also to configure them into one of several circuit modes. These networks have been named polymorphic and can, at least to a measure, account for commonalities in lesion sites, in both affective and schizophrenic diseases. It is proposed that fundamental neuroscience should serve as one of the bases for the classification of psychiatric disorders.
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PMID:Fundamental neuroscience and the classification of psychiatric disorders. 756 51

1. The binding of [3H]-idazoxan in the presence of 10(-6) M (-)-adrenaline was used to quantitate I2 imidazoline-preferring receptors in the rat brain and liver after chronic treatment with various irreversible and reversible monoamine oxidase (MAO) inhibitors. 2. Chronic treatment (7-14 days) with the irreversible MAO inhibitors, phenelzine (1-20 mg kg-1, i.p.), isocarboxazid (10 mg kg-1, i.p.), clorgyline (3 mg kg-1, i.p.) and tranylcypromine (10 mg kg-1, i.p.) markedly decreased (21-71%) the density of I2 imidazoline-preferring receptors in the rat brain and liver. In contrast, chronic treatment (7 days) with the reversible MAO-A inhibitors, moclobemide (1 and 10 mg kg-1, i.p.) or chlordimeform (10 mg kg-1, i.p.) or with the reversible MAO-B inhibitor Ro 16-6491 (1 and 10 mg kg-1, i.p.) did not alter the density of I2 imidazoline-preferring receptors in the rat brain and liver; except for the higher dose of Ro 16-6491 which only decreased the density of these putative receptors in the liver (38%). 3. In vitro, phenelzine, clorgyline, 3-phenylpropargylamine, tranylcypromine and chlordimeform displaced the binding of [3H]-idazoxan to brain and liver I2 imidazoline-preferring receptors from two distinct binding sites. Phenelzine, 3-phenylpropargylamine and tranylcypromine displayed moderate affinity (KiH = 0.3-6 microM) for brain and liver I2 imidazoline-preferring receptors; whereas chlordimeform displayed high affinity (KiH = 6 nM) for these receptors in the two tissues studied, Clorgyline displayed very high affinity for rat brain (KiH = 40 pM) but not for rat liver I2 imidazoline-preferring receptors (KiH = 169 nM). 4. Preincubation of cortical or liver membranes with phenelzine (10-4 M for 30 min) did not alter the total density of I2 imidazoline-preferring receptors, indicating that this irreversible MAO inhibitor does not irreversibly bind to I2 imidazoline-preferring receptors. In contrast, preincubation with 10-6 Mclorgyline reduced by 40% the Bmax of [3H]-idazoxan to brain and liver I2 imidazoline-preferring receptors.5. Chronic treatment (7 days) with the inducers of cytochrome P-450 enzymes phenobarbitone (40 or 80 mg kg-1, i.p.), 3-methylcholanthrene (20 mg kg-1, i.p.) or 2-methylimidazole (40 mg kg-1, i.p.) did not alter the binding parameters of [3H]-idazoxan to brain and liver 12 imidazoline-preferring receptors.The compound SKF 525A, a potent inhibitor of cytochrome P-450 enzymes which forms a tight but reversible complex with the haemoprotein, completely displaced with moderate affinity (KiH = 2-10 microM)the specific binding of [3H]-idazoxan to brain and liver 12 imidazoline-preferring receptors. Preincubation of total liver homogenates with 3 x 10-4 M phenelzine in the presence of 10-3 M NADH, a treatment that irreversibly inactivates the haeme group of cytochrome P-450, did not reduce the density of liver I2 imidazoline-preferring receptors. These results discounted a possible interaction of [3H]-idazoxan with the haeme group of cytochrome P-450 enzymes.6. Together the results indicate that the down-regulation of I2 imidazoline-preferring receptors is associated with an irreversible inactivation of MAO (at least in the brain) that is not related either to the affinity of the MAO inhibitors for I2 imidazoline-preferring receptors or to an irreversible binding to these putative receptors. These findings indicate a novel effect of irreversible MAO inhibitors in the brain and suggest a new target for these compounds that could be of relevance in the treatment of depression, a disease in which an increased density of brain I2 imidazoline-preferring receptors has been reported.
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PMID:The effects of phenelzine and other monoamine oxidase inhibitor antidepressants on brain and liver I2 imidazoline-preferring receptors. 777 44

The effects on behavior and cholinesterase (ChE) of an OP pesticide, dimethoate, were examined in wood mice under laboratory conditions. Mice were administered 0, 5, 15, or 50 mg/kg intraperitoneal dimethoate and their behavior was recorded in an open field for one hour. In a second experiment, using only the 0 and the 50 mg/kg dose, mice were subjected to 10-min open field tests repeated at various time intervals during a 24-h period. Shortly after administration of dimethoate, there was a general, dose-dependent, behavioral depression that was characterized by increased inactivity and decreased grooming, rearing, and sniffing. The introduction of a novel object in the open field failed to elicit any reaction in mice treated with the two highest doses of dimethoate. The behavioral impairment completely disappeared 6 h after treatment. A stereotyped compulsive grooming was also observed in the first 30 min after administration of the two highest doses. Exposure to dimethoate caused a dose-dependent decrease in ChE activity in the brain and in serum. Behavioral impairment was associated with maximum levels of ChE inhibition of 65-75% (brain) and 75-85% (serum). Recovery of ChE activity lagged behind that of behavioral impairment and started 3-6 h after dimethoate administration. The possible implications for free-living wood mice which inhabit cereal fields and may be exposed to OPs are discussed.
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PMID:Behavioral and physiological effects of acute sublethal exposure to dimethoate on wood mice, Apodemus sylvaticus. 868 95

It has been reported that suramin, an anthelminthic, trypanocidal agent and an inhibitor of P2 receptors, may antagonise N-methyl-D-aspartate (NMDA) subtype of the excitatory amino acid receptors. Both NMDA receptors and P2X subclass of P2 receptors are ligand-gated Ca2+-selective channels and, since the increased influx of Ca2+ into neurons has been linked to neurotoxicity, simultaneous inhibition of P2X and NMDA receptors in vivo by suramin could represent an effective neuroprotective treatment. We have found that suramin inhibited the binding of [3H]CGP 39653 to NMDA receptor binding sites in vitro and reduced the frequency of NMDA channel openings in patch-clamp studies. Suramin (1 mM) had no effect on [3H]kainate binding in vitro. In vivo, intracerebroventricular (I.C.V.) injections of suramin (70 nmol/brain) antagonised convulsive effects of the NMDA agonist (RS)-(tetrazol-5-yl)-glycine (TZG, LY 285265). Suramin, however, did not prevent neurotoxic lesions in the hippocampus caused by I.C.V. administration of TZG. Increasing the dose of suramin resulted in death from severe respiratory depression.
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PMID:P2 purinoceptor blocker suramin antagonises NMDA receptors and protects against excitatory behaviour caused by NMDA receptor agonist (RS)-(tetrazol-5-yl)-glycine in rats. 930 84


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