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

1 Synaptic potentials and the responses of frog spinal cord to various acidic amino acids were examined by means of the sucrose gap recording technique. 2 Divalent cations (50-250 microM) specifically antagonized responses evoked at N-methyl-D-aspartate (NMDA) receptors by N-methyl D,L aspartic acid (NMDLA). The rank order of potency was Ni2+ greater than Co2+ greater than Mg2+ greater than Mn2+. Responses to glutamate and aspartate were relatively insensitive to these concentrations of divalent cations. 3 The rank order of potency for divalent ions (1 mM) for antagonism of synaptic transmission in bullfrog sympathetic ganglia was Mn2+ greater than Co2+ greater than Ni2+ greater than Mg2+. Thus synaptic transmission in ganglia was especially sensitive to Mn2+ whereas NMDLA responses were especially sensitive to Co2+ and Mg2+. 4 It was possible to depress selectively the dorsal root-dorsal root potential (DR-DRP) and dorsal root-ventral root potential (DR-VRP) of frog spinal cord using low doses of Co2+ or Mg2+ which did not affect VR-DRP (ventral root-dorsal root potential). It was not possible to produce this selective depression of DR-DRP and DR-VRP with Mn2+, as this cation non-selectively depressed all responses. 5 These results suggest that: (i) divalent cations do not antagonize NMDLA responses by blocking Ca2+ channels which may mediate the response; (ii) postsynaptic NMDA receptors are activated by a neurotransmitter involved in the DR-DRP and DR-VRP pathways but not by any neurotransmitters involved in the VR-DRP pathway; (iii) the neurotransmitter activating NMDA receptors in amphibian spinal cord may be an aspartate-like substance rather than aspartate itself or glutamate.
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PMID:The use of low concentrations of divalent cations to demonstrate a role for N-methyl-D-aspartate receptors in synaptic transmission in amphibian spinal cord. 629 90

The cytotoxic effects of hyperthermia on tumours are readily measured. Parameters of injury to normal tissues are needed to evaluate therapeutic potential. Fifty-five isolated rat livers were perfused in vitro for 180 min in order to determine parameters of hyperthermic injury. During this period they were heated for 1 h at temperatures ranging from 37 degrees to 45 degrees and then assessed for evidence of hyperthermic injury. The most critical indicator of hyperthermic injury was sustained depression of bile production. Bile secretion decreased by 80% after heating at temperatures above 42 degrees. Aspartate amino transferase (AST) release increased significantly at temperatures of 42 degrees and above. Potassium and variable amounts of glucose were released into the medium during heating, reflecting temporary changes in metabolism at high temperatures.
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PMID:Portal vein perfusion of the isolated rat liver: some markers of hyperthermic liver damage. 674 43

The activity of a selective cholecystokinin (CCK)-A receptor agonist, N-acetyl derivative of A71623 (Ac-Trp-Lys(epsilon-N-[2-methylphenylamino-carbonyl]) -Asp-(NMe)Phe-NH2) was investigated in the guinea pig isolated ileum longitudinal muscle myenteric plexus. NAA caused both a phasic and tonic contraction at all concentrations tested (1-1000 nM). The selective CCK-A antagonist L-364,718 (Devazepide) antagonized both types of contraction with a pKB of 10.10 and 9.95, respectively. The CCK-B selective antagonist L-365,260 ((3R(+)-2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1, 4-benzodiazepine-3yl)-N-(3-methylphenyl)-urea) was inactive up to a concentration of 30 nM. Atropine at 300 nM and 1000 nM reduced the maximal response of NAA by only 17% and 50%, respectively. The selective neurokinin (NK)-1 antagonists GR 82334 ([D-pro9[Spiro-gamma-Lactam] Leu10, Trp11]-Phys (1-11)9) at 300 and 1000 nM and (+-) CP-96,345 [(2S, 3S)-cis- 2-(diphenylmethyl)-N- [(2-methoxyphenyl)-methyl] -1-azabici-clo [2.2.2]octan-3-amine] at 10 nM were inactive or partially active. When atropine and GR 82334 or (+/-) CP-96,345 were combined, they produced a dose-dependent synergistic inhibition of both phasic and tonic contractions induced by NAA. The selective NK-3 receptor agonist senktide induced both phasic and tonic contractions that were blocked by tetrodotoxin. In the presence of atropine and GR 82334, both 300 nM, a synergistic depression of the response to senktide similar to that observed for the agonist NAA was disclosed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A further analysis of the contraction induced by activation of cholecystokinin A receptors in guinea pig isolated ileum longitudinal muscle-myenteric plexus. 752 Sep 41

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

Aspartic acid, 5-hydroxyindoleacetic acid, glutamic acid, homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol was determined in samples of ventricular fluid from 82 subjects. Laminar distribution of the total number (Bmax value) of serotonin 1A receptors was determined on seven neurosurgical samples of neocortex. Apart from an association in a small subgroup of subjects between homovanillate concentration and corticosteroid medication, no complicating influences of treatment preceding operation were found. The content of the serotonin metabolite alone was significantly reduced in intractable depressive illness (bipolar and major depressive disorders) compared with neurological conditions subdivided into Alzheimer's disease, other dementias and other conditions. There was no other significant difference between these groups for the compounds measured. The total number of serotonin 1A receptors was highest in the superficial layers, being considerably higher than in the rat, irrespective of cortical layer. This part of the study indicated that these receptors are important for regulating activity of human corticocortical glutamatergic neurons. The results are discussed in relation to treating depression with serotonergic agents and targeting corticocortical glutamatergic neurons as well as acetylcholine in Alzheimer's disease.
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PMID:Antemortem measurements of neurotransmission: possible implications for pharmacotherapy of Alzheimer's disease and depression. 767 42

This study attempts to determine if projections ascending from the guinea pig cochlear nucleus (CN) could be glutamatergic and/or aspartatergic. Multiple radio frequency lesions were made to ablate the right CN. The ablation was verified histologically. To identify the principal targets of CN efferents, silver impregnation methods were used to localize the preterminal degeneration of fibers in transverse sections of the brainstem 5 and 7 days after CN ablation. CN efferents projected heavily to the lateral superior olive (LSO) ipsilaterally, the medial superior olive (MSO) bilaterally, and contralaterally to the medial (MNTB) and ventral (VNTB) nuclei of the trapezoid body, the ventral (VNLL) and intermediate nuclei of the lateral lemniscus and the central nucleus of the inferior colliculus (ICc). There were smaller projections to the lateral nucleus of the trapezoid body ipsilaterally, the dorsal and dorsomedial periolivary nuclei bilaterally, and the dorsal nucleus of the lateral lemniscus contralaterally. There were sparse projections to the VNLL and ICc ipsilaterally and the CN contralaterally, and a very sparse projection to the contralateral LSO. To determine if CN efferents were glutamatergic and/or aspartatergic, the fresh brainstem was sectioned transversely and samples of the LSO, MSO, MNTB, VNLL, and ICc were taken to measure the electrically evoked release and the uptake of D-[3H]Asp and [14C]Gly or [14C]GABA 3-5 days after the CN ablation. The release studies suggest that only certain of the histologically identified projections ascending from the CN may be glutamatergic and/or aspartatergic. CN ablation depressed D-[3H]Asp release in the MSO bilaterally and in the contralateral MNTB and VNLL, suggesting that the CN efferents to these nuclei may use glutamate or aspartate as a transmitter. It was unclear whether a marginal depression of D-[3H]Asp release in the ipsilateral LSO reflected the presence of glutamatergic CN projections to this nucleus. D-[3H]Asp release in the ICc was unaffected, suggesting that CN efferents to this nucleus may not be glutamatergic. There were no deficits in D-[3H]Asp uptake. [14C]Gly release from the LSO and MSO was unchanged. [14C]Gly uptake was unchanged in the MSO and depressed only in the contralateral LSO, possibly reflecting subnormal uptake activity in endings contributed by contralateral MNTB cells that had lost their CN efferents.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Evidence for glutamatergic projections from the cochlear nucleus to the superior olive and the ventral nucleus of the lateral lemniscus. 779 10

Selective CCKA and CCKB receptor agonists and antagonists were used to study the involvement of endogenous cholecystokinin in the behavioural changes that occur in mice in the forced-swimming test (Porsolt's test). The CCKB receptor antagonist, L-365,260 ((3R)-(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl)-3-methylphenylurea), but not the CCKA receptor antagonist, devazepide ((3S)-(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin -3-yl)- 1H-indole-2-carboxamide), elicited an antidepressant-type response (a decrease in the duration of immobility) that was suppressed by previous treatment with either CCK-8 (H-Asp-Tyr(OSO3H)-Met-Gly- Trp-Met-Asp-Phe-NH2) or the selective CCKB receptor agonist BC-264 (Boc-Tyr(SO3H)-gNle-mGly-Trp-N(Me)-Nle-Asp-Phe- NH2). The L-365,260 effect was also prevented by the dopamine receptor antagonist, SCH-23,390 (a dopamine D1-selective receptor antagonist: R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl- 2,3,4,5-tetrahydro-1H-3-benzazepine) and sulpiride (a dopamine D2-selective receptor antagonist: (-)-5-(aminosulfonyl)-N-[(1-ethyl-2-pyrrolidinyl) methyl]-2-metoxybenzamide). On the other hand, co-administration of subthreshold doses of L-365,260 and nomifensine (an atypical antidepressant that selectively blocks dopamine re-uptake mechanisms, 1,2,3,4-tetrahydro-2-methyl-4-phenyl-8-isoquinolinamine) led to a potent antidepressant-type response. These results indicate that blocking of CCKB receptors could result in an increase of extracellular dopamine contents in some brain areas involved in depression and suggest a potential use of CCKB receptor antagonists, alone or combined with antidepressants, in the treatment of depressive syndromes.
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PMID:The CCKB receptor antagonist, L-365,260, elicits antidepressant-type effects in the forced-swim test in mice. 781 46

A 56 year old female patient had acute myocardial infarction which was confirmed by autopsy. However the patient showed no elevation of CK activity in the serum. We proved the deficiency of CK-MM protein in her serum as well as in the myocardial tissues. To further elucidate the molecular mechanism we isolated and characterized genomic DNA and cDNA of CK-MM from the myocardial tissue of the patient and demonstrated the depression of mRNA of CK-MM which might be related with the deficiency of CK-MM protein. Point mutation at codon 54 [Exon 2, GAC (Asp)-->GGC(Gly)] was also demonstrated on the beta-sheet of CK-MM. Association of point mutation with depressed CK-MM is to be clarified.
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PMID:[Acute myocardial infarction without elevation of CK activity: analysis of CK-MM protein and gene of CK-MM]. 788 61


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