Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We showed recently that post-frusemide (furosemide) natriuresis was associated with a major depression of medullary circulation. In the present study, prior to administration of frusemide the tubular transport of NaCl was modified by loading the animals with 5% saline to elucidate a possible interrelation between the tubular and vascular effects of the drug. Moreover, a possible involvement of the renin-angiotensin system was examined by pharmacological blockade using captopril, an inhibitor of angiotensin converting enzyme (1 mg x kg(-1), I.V.), or losartan, a selective inhibitor of angiotensin AT1 receptor (10 mg x kg(-1), I.V.). The effects of frusemide (0.25 mg x kg(-1) I.V., then the same dose given over 1 h) on renal medullary and cortical circulation (using laser-Doppler flowmetry) and renal excretion of sodium (U(Na)V), water and total solutes were measured in anaesthetised rats. With no pre-treatment, frusemide decreased the medullary flow (36.6 +/- 6.0%) significantly more than the cortical flow (10.1 +/- 1.0%; P < 0.001). The difference between the medulla and cortex was not significant in rats which showed high U(Na)V after hypertonic saline loading (2.0 +/- 0.4 vs. 0.4 +/- 0.1 micromol x min(-1) in non-loaded rats): 21.1 +/- 3.9% and 15.8 +/- 1.5%, respectively. At very high U(Na)V (9.5 +/- 1.1 micromol x min(-1)) the post-frusemide decrease in blood flow tended to be smaller in the medulla (7.6 +/- 7.7%) than in the cortex (16.2 +/- 2.6%). The fall in medullary blood flow was attenuated by pre-treatment with captopril (22.0 +/- 3.3%) and abolished by pre-treatment with losartan (2.8 +/- 11.8%). The decrease in cortical blood flow was not changed by hypertonic saline or angiotensin II blockers. The abolition of the post-frusemide depression of medullary blood flow by previous salt loading confirms the proposed link between tubular transport status and vasoconstriction. A similar modification of the response by blockade of the renin-angiotensin system suggests that the system is involved in the mechanism of medullary vasoconstriction.
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PMID:Renal vascular effects of frusemide in the rat: influence of salt loading and the role of angiotensin II. 1157 89

The insertion/(I)/deletion (D) polymorphism of the angiotensin-converting enzyme gene (ACE) is of increasing interest in etiology and treatment of various neuropsychiatric disorders. The present study aimed to replicate own earlier findings that depressive patients with the ACE D-allele are responding better to treatment with antidepressants than those with the II genotype. We further investigated a common polymorphism (A1166C) in the angiotensin II receptor gene (AT1) to examine a possibly combined influence. A sample of 273 patients with major depression, being treated with different classes of antidepressants, was enrolled in the study. Genotyping was carried out using a polymerase chain reaction and snapshot method, respectively, and the severity of depression was monitored using the HAMD-17 scale before and after 4 weeks of treatment. The ACE II genotypes showed poorer improvement in HAMD-17 scale after 4 weeks of treatment (ANOVA: F=4.49, p=0.01) than carriers with one or two D-alleles. Similarly, more than 70% of the AT1 CC homozygotes had a 50% reduction in the HAMD-17 scale within 4 weeks of treatment. Our data might further suggest that patients with a haplotype combining the CC and DD/ID genotypes respond better to treatment than those with either single allele. These results should however be replicated in future research.
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PMID:Genetic variants in the angiotensin I-converting-enzyme (ACE) and angiotensin II receptor (AT1) gene and clinical outcome in depression. 1594 85

Major depressive disorder (MDD) is a debilitating mental disorder with a high prevalence and severe impacts on quality of life. However, the pathophysiological mechanisms underlying MDD remain poorly understood. Here, we used high-performance liquid chromatography with ultraviolet detection-based targeted metabolomics to identify amino acid changes in the small intestine, in a rat model of chronic unpredictable mild stress (CUMS). Pearson's correlation analysis was conducted to investigate the correlations between amino acid changes and behavioral outcomes. Western blot analysis was employed to verify intestinal amino acid transport function. Moreover, we performed an integrated analysis of related differential amino acids in the hippocampus, peripheral blood mononuclear cells (PBMCs), urine and cerebellum identified in our previous studies using the CUMS rat model to further our understanding of amino acid metabolism in depression. Decreased concentrations of glutamine and glycine and upregulation of aspartic acid were found in CUMS model rats. These changes were significantly correlated with depressive-like behaviors. Western blot analysis revealed that CUMS rats exhibited a reduction in the expression levels of amino acid transporters ASCT2 and B0AT1, as well as an increase in LAT1 expression. Impaired transport of glycine and glutamine into the small intestine may contribute to a central deficiency. The current findings suggest that the glycine and glutamine uptake systems may be potential therapeutic targets for depression. The integrated analysis strategy used in the current study may provide new insight into the cellular and molecular mechanisms underlying the gut-brain axis, and help to elucidate the pathophysiological changes in central and peripheral systems in depression.
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PMID:Effects of chronic stress on intestinal amino acid pathways. 3083 Nov 84