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)

Previous studies from this laboratory have demonstrated that growth of the methylcholanthrene (MCA) sarcoma is dependent on total nitrogen substrate availability in vivo and on the specific amino acids asparagine and glutamine in vitro. This experiment determines whether these two phenomena can be used to selectively depress tumor growth and maintain host carcass. Sixty-two rats were inoculated with sarcoma and were infused for 10 days with isocaloric (60 kcal/day) TPN solutions at 100%, 16%, 10%, and 5% of normal nitrogen levels, either with (W) or isonitrogenously without (WO) the amino acids asparagine, glutamine, aspartic acid, and glutamic acid. W solutions contained 33% of these amino acids. Mean weights of 100 W tumors were significantly greater (p = 0.002) than all other groups. Total body weights minus tumor weights were similar in W versus WO animals at each rate of nitrogen infusion. Mean venous plasma concentrations of asparagine, aspartic acid, glutamine, and glutamic acid were similar in all eight groups. These data indicate that the same degree of tumor depression produced by nitrogen deprivation can also be produced by removal of asparagine, glutamine, and their precursors from nutrient solutions without adverse effects on carcass mass. The mechanisms involved are not readily explained by analysis of venous plasma amino acid concentrations.
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PMID:Influence of total nitrogen, asparagine, and glutamine on MCA tumor growth in the Fischer 344 rat. 289 15

beta-Pyrazol-1-yl-DL-alanine, an uncommon amino acid from plants of the Cucurbitaceae, was fed to mice. Although pyrazole is known to affect the liver enzymes UDP-glucose dehydrogenase, UDP-glucuronyl transferase and UDP-glucuronic acid pyrophosphatase, and also depresses their liver glycogen concentrations, beta-pyrazol-1-ylalanine had no such effects. beta-Pyrazol-1-ylalanine could not be detected in the liver of the experimental animals but was present in the urine. No other change in urinary amino acid content was observed. Studies with [14C]-beta-pyrazol-1-yl-DL-alanine showed the administered amino acid was excreted over a 4-day period, 93% of the compound supplied was recovered. Similar recoveries were obtained with the L-enantiomer from cucumber seed. The metabolic inertness of beta-pyrazol-1-ylalanine was also apparent in experiments involving subcutaneous injection of this compound. Administration of pyrazole confirmed an earlier report of resultant increased activity of liver UDP-glucose dehydrogenase and UDP-glucuronyl transferase, and of the depression of activity of liver UDP-glucuronic acid pyrophosphatase. A concomitant 40% decrease in liver glycogen content was seen. The urine contained a novel metabolite, identified as a peptide conjugate of a pyrazole derivative. Mass spectrometry and p.m.r. spectroscopy indicate that this derivative is 3,4,4-trimethyl-5-pyrazolone. The amino acid constituents are aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine and leucine. The urine of mice receiving pyrazole contained less free glycine and alanine than controls. From the results, it is concluded that pyrazole is not a catabolite of dietary beta-pyrazol-1-ylalanine but to the contrary, the amino acid is essentially excreted unchanged. Formation of 3,4,4-trimethyl-5-pyrazolone from pyrazole would imply C-methylation, a process that has not been previously observed in a mammalian detoxication context.
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PMID:Metabolism of the amino acid beta-pyrazol-1-ylalanine and its parent base pyrazole. 298 41

The effect of asphyxia and subsequent resumption of respiration on the content of adenine nucleotides and some amino acids in heart tissue and mitochondria, as well as respiration of heart mitochondria was studied in rats. The depression of cardiac contractile function during asphyxia showed a better correlation with losses in mitochondrial adenine nucleotides (ATP + ADP + AMP) than those in cardiac tissue. The decrease in the heart work index was accompanied by a decrease in state 3 respiration with glutamate and malate as well as uncoupled respiration with these substrates. This did not occur with succinate. Nonphosphorylating (state 4) respiratory rates and ADP/O ratios were slightly affected by asphyxia, when respiratory substrates of both types were used. The decreased level of glutamic acid in the tissue and mitochondria of asphyxic hearts was simultaneously observed with a significant increase of alanine in cardiac tissue and of aspartic acid in the mitochondria. The losses of intramitochondrial ATP and respiratory activity with NAD-dependent substrates during asphyxia were associated with a reduction of glutamic acid level in mitochondria. The recovery of cardiac function during resumption of respiration was related to the restoration of mitochondrial respiration supported by glutamate and malate, as well as to the restoration of mitochondrial adenine nucleotides and glutamic acid. The results suggest that the depression of cardiac function caused by acute respiratory hypoxia may be attributed to impairment of electron transport, particularly in complex I of the respiratory chain and changes in metabolism of glutamic acid.
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PMID:The relationship between the cardiac contractile function, adenine nucleotides and amino acids of cardiac tissue and mitochondria at acute respiratory hypoxia. 361 64

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

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

The aim of this investigation was to determine the incidence of seizure activity in the acute phase following traumatic brain injury. Compression contusion trauma was produced in the right parietal cortex in 19 artificially ventilated rats. Electroencephalographic recordings were carried out in 17 of the animals for 2 h following the impact. The extracellular levels of neuroactive amino acids were simultaneously monitored in 9 of the experiments using microdialysis. In 14 of the 17 animals a generalized seizure activity with an average duration of 59 s (range 30-101 s) was recorded. The mean time lag between trauma and seizure onset was 67 s (range 26-90 s). The seizure activity was consistently followed by post-ictal depression. The trauma was accompanied by a transient increase of aspartate, taurine, glutamate and glycine, in decreasing rank order. The seizure activity occurred when the levels of these neuroactive amino acids were elevated. It is concluded that the high incidence of seizure activity observed may be an important factor contributing to secondary ischemia after traumatic brain injury. Aspartate and glutamate, potentiated by glycine, may play a role in post-traumatic seizure activity.
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PMID:Epileptic seizure activity in the acute phase following cortical impact trauma in rat. 818 Aug


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