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)

We studied the effects of polymorphonuclear leukocytes (PMNLs) activated by N-formyl-methionyl-leucyl-phenylalanine on the endothelium-dependent relaxation of the rabbit basilar artery (BA). In the presence of activated PMNLs the maximal vessel relaxation to acetylcholine (ACh) and bradykinin (endothelium-dependent dilators) was decreased from 62 +/- 7 and 48 +/- 6% to 23 +/- 9 and 19 +/- 7, respectively, (p < 0.05). The endothelium-independent relaxation to nitroprusside was not affected by PMNLs. When PMNLs were activated in the organ chamber in the presence of a low concentration of platelet-activating factor (PAF, 10(-10) mol/l), the depression of ACh- and bradykinin-induced relaxation increased by 27 +/- 9 and 23 +/- 7%, respectively (p < 0.05), though at this concentration PAF alone did not cause PMNLs to induce endothelial dysfunction. In addition, in the presence of PAF, activated PMNLs inhibited endothelium-dependent relaxation at lower cell concentrations and shorter periods of contact with the endothelium. PMNL effects on the endothelium were correlated with the level of cell exocytosis as tested by accumulation of beta-glucuronidase activity. In the presence of PAF, accumulation of this activity increased from 46 +/- 6 to 79 +/- 8 U/ml (p < 0.05). Examination of BA segments by scanning electron microscopy revealed that, after the treatment with activated PMNLs, the endothelium was morphologically preserved, but in the presence of PAF PMNLs caused more apparent microlesions in the endothelial layer. We conclude that small quantities of PAF potentiate the activation of marginated PMNLs. These cells then become more aggressive towards the endothelium, producing significant depression of the endothelium-dependent relaxation.
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PMID:Leukocyte-induced endothelial dysfunction in the rabbit basilar artery: modulation by platelet-activating factor. 755 83

Most studies on the pathological responses of the heart to ethanol have been conducted in isolated systems. The objectives of this study were to determine (1) the synthesis rate of ventricular mitochondrial proteins in vivo and (2) whether the synthesis rates of these proteins are perturbed by acute ethanol exposure in vivo. Fractional rates of protein synthesis [defined as the percentage of tissue protein renewed each day; i.e., ks (%/day)] were determined in male Wistar rats by in vivo injection of a flooding dose of L-[4-3H] phenylalanine. Subsarcolemmal mitochondria were released by polytron treatment, and the isolation of interfibrillar mitochondria involved treatment of the cardiac homogenate with the proteolytic enzyme Nagarse. In the control rats mean ks values of 22.4%/day were observed for mixed cardiac proteins. The synthesis rates of subsarcolemmal and interfibrillar mitochondrial proteins were lower, i.e., 16.9%/day and 10.9%/day, respectively. Acute ethanol administration (75 mmol/kg body weight ip, 2.5 hr) depressed the fractional rate of protein synthesis in all cardiac fractions, including those pertaining to the mitochondria, as follows: mixed fraction--21%, p < 0.01; subsarcolemmal mitochondria--23%, p < 0.01; interfibrillar mitochondria--26%, p < 0.05; and nuclear fraction--20%, p < 0.05. In conclusion, the reduced synthesis rate of the mitochondrial proteins in response to acute ethanol exposure may in some way be partly connected with the depression in myocardial contractility and associated functional damage of mitochondrial metabolism.
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PMID:Synthesis of ventricular mitochondrial proteins in vivo: effect of acute ethanol toxicity. 769 59

Whole-cell voltage-clamp technique was used to examine the effects of a mu-opioid receptor agonist DAGO (Tyr-D-Ala-Gly-Me-Phe-Gly-ol-enkephalin) on GABA-induced currents in acutely isolated spinal dorsal horn (DH) neurons from laminae I-IV of young rats. We found that a bicuculline-sensitive GABA-induced current was potentiated by DAGO (0.5-500 nM), in a dose-dependent manner, in approximately 62% of the tested cells. The elevated GABA responses outlasted the period of DAGO application, and either recovered within 10 min after the removal of the peptide or persisted for up to 50 min. The potentiating effect of DAGO was reduced or prevented by naloxone and the mu-opioid receptor-selective antagonist beta-funaltrexamine. A similar enhancing effect on the membrane currents activated by administration of muscimol, a GABAA receptor-specific agonist, was produced by DAGO. In addition, a transient depression of GABA responses was observed in approximately 25% of the cells tested. These results indicate that the mu-opioid agonist DAGO modulates the sensitivity of postsynaptic GABAA receptors in a large proportion of spinal neurons from laminae I-IV, with the major effect being facilitation. The DAGO action could contribute to the regulation of the strength of primary afferent neurotransmission, including nociception.
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PMID:Activation of mu-opioid receptor modulates GABAA receptor-mediated currents in isolated spinal dorsal horn neurons. 770 May 61

Disturbances of serotonergic pathways have been implicated in a wide variety of neuropsychiatric disorders such as depression, anxiety, migraine, and substance abuse. Genetic variation in genes coding for serotonin receptor proteins might well be involved in the genetic predisposition to these diseases and/or of pharmacogenetic relevance. Genomic samples from 46 unrelated healthy subjects were investigated by single-strand conformation analysis (SSCA) to screen for genetic variation in the human serotonin 1D beta (5-HT1D beta) receptor gene. Overlapping PCR (polymerase chain reaction) fragments covered the whole coding sequence as well as 5' untranslated regions of the 5-HT1D beta gene. Four nucleotide sequence variants were found: a coding mutation in nucleotide position 371 which leads to an amino acid exchange (Phe-->Cys) in position 124 of the receptor protein and three mutations in the 5' flanking region. For all mutations specific PCR-based assays were developed which allow rapid genotyping in populations and families. To our knowledge, the Phe-124-Cys substitution is the first natural occurring molecular variant which has been identified for the 5-HT1D beta receptor so far.
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PMID:Identification of genetic variation in the human serotonin 1D beta receptor gene. 780 50

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

The effect of insulin and leucine on amino acid and protein metabolism in muscle is not fully understood. To characterize their separate and combined effects on free amino acids in muscle and plasma, 11 volunteers received an infusion of either leucine (1 g h-1, Group 1) or glucose (20 g h-1, Group 2) for 2 h followed by a combination of the two infusions for an additional 2-h period. In muscle both the leucine infusion and the leucine plus glucose infusion increased the concentration of free leucine significantly, while the sum of the other branched chain amino acids (BCAA), of the aromatic amino acids and of the basic amino acids decreased. Glucose infusion alone decreased the sum of the essential amino acids, the BCAA and the aromatic amino acids. The combination of leucine and glucose augmented the decreases, while the concentrations of glutamate, glutamine and alanine were unaffected. In plasma the leucine infusion doubled the leucine concentration and decreased alanine, valine, methionine, tyrosine, phenylalanine and the sum of the aromatic amino acids. Glucose infusion decreased methionine, serine, isoleucine and the sum of the essential amino acids and of the BCAA. The combination of leucine infusion and hyperinsulinaemia augmented the decreases. The plasma concentrations of the keto acids of valine and isoleucine decreased by the leucine infusion while the concentrations of the keto acid of leucine and isoleucine decreased by glucose infusion. The combination of leucine and glucose had an additive effect. These effects are attributed to a specific effect of leucine on the other two BCAA and a depression of muscle proteolysis by both leucine and insulin, resulting from glucose infusion.
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PMID:The separate and combined effect of leucine and insulin on muscle free amino acids. 782 Sep 76

Cell adhesion molecules play important roles in axon guidance and synapse formation. Recent studies suggest that the expression of some of these molecules can be regulated either by electrical activity or by specific neurotransmitters. The expression of neural cell adhesion molecule (NCAM)-like molecules in Aplysia, designated apCAM, is downregulated from the surface of sensory neurons by 5-HT, a transmitter known to evoke long-term changes in the structure and function of these neurons. We tested whether the distribution of apCAM on the surface of other neurons can be regulated by treatments with other neurotransmitters known to evoke long-term functional and structural changes in Aplysia neurons, and we examined the consequences of treatments with the neurotransmitters on the pattern of growth cone-neurite interactions. We report that applications of the neuropeptide Phe-Met-Arg-Phe-amide (FMRFamide) that evoke long-term synaptic depression also reduce apCAM expression on the surface of motor cell L7 via a mechanism that appears to be similar to the mechanism mediating the 5-HT-induced change in the sensory cells. Specific treatments that affect apCAM distribution on the surface of their respective cells, 5-HT on sensory cells or FMRFamide on motor cell L7, mimic treatment with monoclonal antibodies against apCAM by evoking a significant reduction in the fasciculation of growth cones with other neurites extending from homologous cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decrease in growth cone-neurite fasciculation by sensory or motor cells in vitro accompanies downregulation of Aplysia cell adhesion molecules by neurotransmitters. 790 62

Serum phenylalanine and tyrosine levels were measured in 26 patients with severe depression before and after receiving electroconvulsive therapy. The phenylalanine:tyrosine [P:T] ratio declined significantly for those responding to treatment but not for nonresponders. These findings are discussed in relation to tetrahydrobiopterin, the essential cofactor for the formation of noradrenaline, dopamine and serotonin and the hydroxylation of phenylalanine to tyrosine.
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PMID:Recovery from depression after electroconvulsive therapy is accompanied by evidence of increased tetrahydrobiopterin-dependent hydroxylation. 797 41

Mastoparan B is a cationic, amphiphilic tetradecaeptide (LKLKSIVSWAKKVL-CONH2) isolated from the venom of the hornet Vespa basalis. Intravenous injection of the peptide into rats caused a profound depression of blood pressure and cardiac function, which was inhibited by cyproheptadine, reserpine and multiple doses of compound 48/80, but not by diphenhydramine and cromolyn. Mastoparan from Paravespula lewisii showed little cardiovascular inhibitory activity. A synthetic mastoparan B analog in which lysine at position 2 was replaced by asparagine showed a marked decrease in the cardiovascular depressor effects, while replacing lysine at position 4, 11 or 12 with leucine did not cause a significant reduction in these effects. Replacing lysine at position 12 with leucine even caused a more sustained depressor effect. However, the analog in which lysines at positions 11 and 12 were replaced by leucine lost its cardiovascular inhibitory activity. Replacing tryptophan at position 9 with phenylalanine in mastoparan B did not affect its activity. It is concluded that mastoparan B is involved in the cardiovascular disturbances induced by the hornet venom. Lysine at position 2 is a critical residue for the cardiovascular effects of mastoparan B. A peptide molecule with two lysine residues, one located close to the amino terminus and the other near the carboxyl end of the peptide, appears to be the optimal structure for eliciting the cardiovascular depressor effects.
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PMID:Cardiovascular effects of mastoparan B and its structural requirements. 798 52

Cerebral serotonin is synthetized from its blood precursor: tryptophan (TRP), an essential amino acid (6). TRP has been extensively studied since serotonine has been reported to be involved in the pathogenesis of depression (9). In one hand, brain serotonin content depends on regulation by plasma large neutral amino acids (LNAA): leucine, isoleucine, valine, tyrosine and phenylalanine that compete with TRP to cross over the blood brain barrier (7, 13). In the other hand TRP is largely linked with albumin. So, we have studied plasma total TRP, free TRP and the ratio TRP on LNAA as potential cerebral serotonin index. The aim of this study is to observe the blood variations of the biological parameters in fasting and postprandial conditions in 8 depressed women, aged from 57 to 78 years, on a short protein controlled diet: 4 women had TRP poor then rich diet and the others 4 rich then poor. Alimentary proteins modulated diets and each patient was his own control: the results under modulated diet were compared with those under normal diet at the same time. More over, 2 psychotic patients aged 58 and 70 years have been studied at the same time, in each group. Biological datas were compared with clinical evolution.
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PMID:[Plasma tryptophan in a protein controlled diet in depressed patients]. 808 36


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