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)

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

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

Serotonin 5-hydroxytryptamine (5-HT)2 receptors are implicated in the etiology of mental disease and depression. Drugs that interact with the 5-HT2 receptor are used therapeutically to treat such illnesses, and their mechanisms of action are of great interest. In this study 5-HT2 receptor-ligand interactions were examined by site-directed mutagenesis in which three aspartic acid to asparagine mutants (Asn-120, Asn-155, and Asn-172) were created and expressed in NIH3T3 cells. The Asp-120 to asparagine mutant exhibited the same affinity for 125I-lysergic acid diethylamide (125I-LSD) as did the wild-type receptor and showed a decreased and GTP-insensitive binding affinity for the agonists 5-HT and (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane (approximately 10-fold) and the antagonists ketanserin and mianserin (approximately 10-fold) but not spiperone. The mutation also abolished agonist-stimulated formation of [3H]polyphosphoinositides (PI). The Asn-155 mutant showed reduced binding affinity for 125I-LSD (Kd, 2.8 nM versus 0.6 nM for the wild-type receptor) and had reduced affinity for agonists (approximately 30-fold) and for antagonists (14-75-fold). However, the Asn-155 receptor retained GTP sensitivity and the ability to stimulate PI formation. The Asn-172 mutant retained the wild-type Kd value for 125I-LSD, exhibited only approximately 5-fold reduced affinity for 5-HT and (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane while retaining GTP-sensitive agonist binding showed no change in affinity for ketanserin, and had a small decrease in mianserin and spiperone binding (approximately 6-fold). The Asn-172 receptor also retained the ability to form PI. These results indicate that Asp-120 is necessary for allosteric activation of the guanine nucleotide-binding protein. Asp-155 is necessary for high affinity binding, probably by acting as a counterion for the amine group of the ligand. The different effects of the three mutations on ketanserin, mianserin, and spiperone binding affinity suggest that these antagonists may share overlapping but different binding domains. The information provided by this study may facilitate the design of therapeutic site-selective compound based on the structure of the 5-HT2 receptor.
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PMID:Site-directed mutagenesis of the serotonin 5-hydroxytrypamine2 receptor: identification of amino acids necessary for ligand binding and receptor activation. 831 24

Aspartic acid (580 mg/kg, SC) causes a long-lasting depression of ventilation in adult male, but not female rats. The purpose of these experiments was to determine if the aspartic acid-induced depression of ventilation in awake male Sprague-Dawley rats is a consequence of the release of endogenous opioids or somatostatin. These neuromodulators have been shown to cause depression of ventilation. Pretreatment of male rats with the opioid antagonist naloxone (5 mg/kg) 10 min prior to aspartic acid attenuated the drop of ventilation from -138.6 +/- 26.9 ml/min to -63.4 +/- 16.6 ml/min (p < 0.01) by affecting both tidal volume and frequency of breathing. Naloxone administered prior to saline had no effect on ventilation. In another experiment, cysteamine (100 mg/kg), a somatostatin depleter, injected SC 2 h before aspartic acid administration also attenuated depression of ventilation by affecting frequency of breathing. Cysteamine alone, compared to saline, had no effect on ventilation over 24 h. These results suggest that aspartic acid acts by releasing endogenous opioids and somatostatin.
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PMID:Cysteamine and naloxone attenuate aspartic acid-induced depression of ventilation. 877 56

Subcutaneous administration of aspartic acid results in a long-lasting but reversible depression of ventilation in male but not in female rats. Aspartic acid acts on N-methyl-D-aspartate receptors. The present study tested the hypothesis that a noncompetitive N-methyl-D-aspartate-receptor antagonist, dextromethorphan (Dex), would depress ventilation in female rats and stimulate it in male rats. Moreover, Dex administered prior to aspartic acid should prevent the aspartic acid-induced depression of ventilation in male rats. In female rats, Dex caused a 30% depression of ventilation relative to saline at 5 and 10 mg/kg (P < 0.01) but not at the highest dose (20 mg/kg). In male rats, Dex had no effect on ventilation. At a dose of 20 mg/kg, Dex depressed oxygen consumption to 50% of the saline value at all time points in female rats (P < 0.001) and in male rats 45 and 60 min after administration. The time points when Dex depressed ventilation and oxygen consumption were different in female rats, suggesting that the depression of ventilation was not the result of a depression in oxygen consumption. During a hypercapnic challenge (7% CO2), female rats treated with 5 and 10 mg/kg of Dex exhibited a smaller increase in ventilatory response relative to saline treatment. At a dose of 20 mg/kg, the hypercapnic responsiveness of male rats was markedly stimulated (85.8 +/- 8.95 ml/min) relative to saline (50.6 +/- 9.14 ml/min; P < 0.001). Finally, Dex administered before aspartic acid prevented the aspartic acid-induced depression of ventilation in male rats. Thus, in rats, Dex has gender-specific effects on ventilation and these effects are not associated with changes in oxygen consumption.
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PMID:Dextromethorphan affects ventilation differently in male and female rats. 894 9

Ventilation, oxygen consumption, the ventilatory equivalent for oxygen, and ventilatory responses to hypoxia and to hypercapnia were evaluated in conscious male rats who received each of four treatments: (1) microinjection of artificial cerebrospinal fluid (aCSF) into the arcuate nucleus and subcutaneously saline (CS); (2) aspartic acid into the arcuate nucleus and saline subcutaneously (AS); (3) aCSF into the arcuate nucleus and naloxone subcutaneously (CN); and (4) aspartic acid into the arcuate nucleus and naloxone subcutaneously (AN). Rats treated with CN exhibited a depression of ventilation, ventilatory equivalent, ventilatory response to hypercapnia, and tidal volume response to hypoxia and to hypercapnia. AS had no effect on any parameters. Administration of both aspartic acid and naloxone attenuated all the effects of CN except the depression of minute ventilation in response to hypercapnia. Therefore the naloxone (a mu opioid receptor antagonist) induced a depression of ventilation that was attenuated by aspartic acid acting on N-methyl-D-aspartic acid receptors in the arcuate nucleus.
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PMID:Aspartic acid in the arcuate nucleus attenuates the depressive effects of naloxone on ventilation. 986 84

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


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