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)

During pentobarbital (25 mg/kg i.v. in 2 min), pentothal (15 mg/kg i.v. in 2 min) and ketamine (10 mg/kg i.v. in 2 min) narcosis, rabbits showed reduced platelet reactivity ot the direct aggregating effect of ADP (2 X 10(-5) M) and the indirect effect of thrombin (0.1 U/ml). Certain arousal drugs, specifically those of metabolic type such as SAMe (20 mg/kg i.v. in 2 min) and Thiola (166 mg/kg i.v. in 2 min) and of haemodynamic type such as nicergoline (6.66 mg/kg i.v. in 2 min) and hexobendine (5 mg/kg i.v. in 2 min) administered 31 min after narcosis induction, impede the depression brought on by narcosis on on platelet reactivity.
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PMID:[Narcosis, platelet aggregation and arousing drugs]. 68 73

The synthesis of at least six enzymes implicated in methionine biosynthesis in Saccharomyces cerevisiae is regulated pleiotropically by two independent regulatory systems. Repression of enzyme synthesis is promoted either by exogenous methonine or by exogenous S-adenosylmethionine (SAM). The regulatory system acting in methionine mediated repression seems to comprise methionyl-tRNA-met as a co-repressor and the other system, acting in SAM repression, comprises SAM as a co-repressor. This concept gives a role in regulation to the two activated forms of methionine. Moreover, evidence is presented that the "SAM repressor" probably acts at a post-transcriptional level while the "met-tRNAmet repressor" would be active at the transcriptional level. These conclusions have been based on two series of experiments: one using a mutant bearing a modified methionyl-tRNA synthetase [L-methionine: tRNA-met ligase (AMP-forming) E.C.6.1.1.10] and one studying the kinetics of depression of synthesis of one of the biosynthetic enzymes after repression either by exogenous methionine or by exogenous SAM. Our results are strengthened by the use of two different drugs: one inhibiting messenger RNA synthesis and the other inhibiting protein synthesis.
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PMID:Regulation of methionine synthesis in Saccharomyces cerevisiae operates through independent signals: methionyl-tRNAmet and S-adenosylmethionine. 78 67

Phospholipid methylation was quantified in non-diabetic and streptozotocin diabetic rat erythrocytes. While the total mass of methylated lipids remained the same in both groups, the relative abundance of individual methylated lipid species differed significantly in diabetic erythrocytes. Moreover, incubation of erythrocytes membranes with S-adenosyl methionine, a substrate for methyl transferases, not only increased membrane lipid methylation but also decreased Na+, K+ ATPase activity significantly. These results suggest that phospholipid methylation may cause the observed depression of erythrocyte Na+, K+ ATPase activity in diabetes and could contribute to the altered rheology of erythrocytes in diabetes.
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PMID:Phospholipid N-methylation in diabetic erythrocytes: effects on membrane Na+, K+ ATPase activity. 132 Oct 9

Hepatic cysteine sulfinic acid decarboxylase (EC 4.1.1.29) activity has been reported to decrease in response to both L-methionine (Met) feeding and adrenalectomy in rats. A series of experiments was conducted to (a) determine if CSAD depression was evident in female rats fed a methionine-supplemented diet; and (b) determine if adrenal hormones mediated the response of CSAD to dietary methionine. Cysteine sulfinic acid decarboxylase (CSAD) activity was measured in livers of male and female rats fed a methionine-supplemented diet. In female rat liver, CSAD activity was only 25% of the activity measured in livers of male rats. Hepatic enzyme activity in male rats fed a casein-based basal diet containing 0.6% L-methionine was 2.5-fold higher than activity in male rats fed a methionine-supplemented diet containing 1.35% L-methionine (+Met). Similarly, enzyme activity in livers of female rats fed the basal diet was 1.7-fold higher than in female rats fed a methionine-supplemented diet. CSAD activity in adrenalectomized (ADX) male rats fed the basal diet was depressed (990 +/- 120 nmol/min.g liver) compared to activity in intact controls (2347 +/- 89) and sham controls (2040 +/- 143) fed the basal diet. CSAD activity was further depressed in ADX, intact controls, and sham controls fed +Met. Immunochemical detection and quantification of CSAD protein in rat liver demonstrated that changes in CSAD protein were consistent with the observed decreased enzyme activity in female rats, ADX rats, and rats fed +Met. S-Adenosylmethionine and S-adenosylhomocysteine concentrations tended to increase in livers of rats fed +Met. ADX rats fed +Met had the greatest increase in S-adenosylmethionine and S-adenosylhomocysteine concentrations. The depression in hepatic CSAD observed after feeding +Met to rats does not appear to involve adrenal function.
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PMID:Quantification of cysteine sulfinic acid decarboxylase in male and female rats: effect of adrenalectomy and methionine. 156 10

S-adenosylmethionine is a relatively new anti-inflammatory drug with analgesic and anti-depressant effects. Efficacy of 800 mg orally administered s-adenosylmethionine daily versus placebo for six weeks was investigated in 44 patients with primary fibromyalgia in double-blind settings. Tender point score, isokinetic muscle strength, disease activity, subjective symptoms (visual analog scale), mood parameters and side effects were evaluated. Improvements were seen for clinical disease activity (P = 0.04), pain experienced during the last week (P = 0.002), fatigue (P = 0.02), morning stiffness (P = 0.03) and mood evaluated by Face Scale (P = 0.006) in the actively treated group compared to placebo. The tender point score, isokinetic muscle strength, mood evaluated by Beck Depression Inventory and side effects did not differ in the two treatment groups. S-adenosylmethionine has some beneficial effects on primary fibromyalgia and could be an important option in the treatment hereof.
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PMID:Oral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluation. 192 18

Male rats were fed sulfur and nonsulfur amino acid-supplemented diets, and the response of cysteine sulfinic acid decarboxylase (CSAD) activity was determined. After adaptation to a casein-based basal diet, rats were fed diets containing additions of L-methionine. Hepatic CSAD activity decreased in a dose-dependent manner. Significant depression of CSAD activity in liver was evident within 24 h of feeding rats a methionine-supplemented diet. Depression of enzyme activity was reversed upon refeeding the basal diet. After rats were fed diets supplemented with methionine, cystine, homocystine, S-methyl-L-cysteine, phenylalanine, leucine, or ethionine for 14 days, hepatic CSAD activity in rats fed S-methyl-L-cysteine-, phenylalanine-, or leucine-supplemented diets was not depressed compared with activity in rats fed a basal diet. In contrast, CSAD activity in livers of rats fed cystine-, homocystine-, methionine-, or ethionine-supplemented diets was 60, 40, 40, and 8%, respectively, of the activity in livers from control rats. Immunochemical detection and quantification of CSAD protein in rat liver indicated that CSAD protein concentration was correlated to CSAD activity. CSAD activity may be specifically regulated by sulfur amino acids metabolized by the S-adenosylmethionine-dependent pathway of methionine metabolism.
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PMID:Dietary sulfur amino acid modulation of cysteine sulfinic acid decarboxylase. 195 78

Methylation has been implicated in the etiology of psychiatric illness. Parenteral S-adenosylmethionine, a methyl group donor, has been shown to be an effective antidepressant. The authors studied the antidepressant effect of oral S-adenosylmethionine in a randomized, double-blind, placebo-controlled trial for 15 inpatients with major depression. The results suggest that oral S-adenosylmethionine is a safe, effective antidepressant with few side effects and a rapid onset of action. S-Adenosylmethionine induced mania in a patient with no history of mania. S-Adenosylmethionine may be useful for patients who cannot tolerate tricyclic anti-depressants. These findings support a role for methylation in the pathophysiology of depression.
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PMID:Oral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trial. 218 33

S-Adenosyl-L-methionine (AdoMet) is a safe and probably effective antidepressant agent in certain forms of clinical depression. This article presents a new hypothesis to account for the mechanism of action of S-adenosylmethionine in such illnesses, based upon the known biochemistry of this compound, and upon current knowledge of clinical and genetic aspects of affective disorders. Giulio Cantoni, S. Harvey Mudd and V. Andreoli postulate that at least some major mood disorders are due to abnormalities affecting the AdoMet-dependent methylation of a substance in the CNS. For convenience and without prejudging the chemical structure of this substance, they call it 'barinine'. The model requires that barinine be subject to AdoMet-dependent methylation and that methylbarinine be subject to metabolic demethylation to regenerate the original barinine. Methylbarinine should be mood elevating, whereas barinine itself should not be. Depression is a result of abnormalities lowering the normal steady-state concentration of methylbarinine, whereas mania results from an abnormal elevation of methylbarinine.
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PMID:Affective disorders and S-adenosylmethionine: a new hypothesis. 248 Jun 71

With the aim of assessing four forms of therapy with adjustment-disordered outpatients, we randomly assigned 70 subjects to the following treatments: supportive psychotherapy (psychoanalytically oriented), viloxazine (an antidepressant), lormetazepam (a benzodiazepine), and S-adenosylmethionine (a methyl donor with antidepressive properties). A further group of 15 subjects received a placebo, orally administered. The trial lasted 4 wk. None of the treatments had clearly superior effects over others on scores on the Zung Self-rating Depression Scale. All produced a significant improvement. However, groups given S-adenosylmethionine and supportive psychotherapy had the highest mean scores.
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PMID:Treatment of adjustment disorders: a comparative evaluation. 264 47

During open trials of intravenous and oral S-adenosyl methionine (SAM) and a placebo-controlled trial of intravenous SAM in 29 patients, 25 patients had SAM and four had placebo (27 courses of SAM, two of the patients receiving two trials a piece). Nine of 11 bipolar patients (all SAM-treated) switched into elevated mood state (hypomania, mania and euphoria) and two did not respond. Six endogenous unipolar patients improved and five did not. No non-endogenous patient or placebo patient responded for more than 14 days. No unipolar patient switched into elated mood. In eleven (38%) trials and nine (33%) patients there was a switch from depression to elation. Biochemical data from the cerebrospinal fluid of eight patients suggested that the role of the dopaminergic system should be further explored.
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PMID:The switch mechanism and the bipolar/unipolar dichotomy. 263 13


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