Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When mouse lymphoma cells (L-1210) are treated with methylnitrosourea, a DNA-damaging agent, polyadenosine diphosphoribose (poly(ADP-ribose)) synthetase activity increases 5-8-fold in 2-3 h, while RNA polymerase activity remains constant for an initial 2 h and then gradually decreases to 25-30% of the control level in 5 h. Both alpha-amanitin-sensitive and -resistant RNA polymerase activities are depressed to the same degree by the treatment with methylnitrosourea. The depression in RNA synthesis is virtually prevented when the treated cells are cultured in the presence of 3-aminobenzamide, a specific inhibitor of poly(ADP-ribose) synthetase. Analyses of the RNA extracted from the cells labeled with [3H]uridine by agarose gel electrophoresis and by poly(U)-Sepharose column chromatography show that the contents of ribosomal precursor RNA and poly(A)-containing RNA are both low in the methylnitrosourea-treated cells as compared with those in the untreated cells and that the reduction in the contents of these kinds of RNA is almost completely prevented by the addition of 3-aminobenzamide to the culture medium. These results suggest that the enhancement of poly(ADP-ribosyl)ation causes the decrease in both synthesis of ribosomal RNA and messenger RNA.
 ...
PMID:Participation of poly(ADP-ribosyl)ation in the depression of RNA synthesis caused by treatment of mouse lymphoma cells with methylnitrosourea. 617 37

The effect of ATP synthesis on delta mu H in rat liver mitochondria has been analyzed by separating the steps of adenine nucleotide translocation and ATP synthesis in the matrix. Either exchange of ATP, synthesized by substrate level phosphorylation in the matrix of oligomycin-treated mitochondria, for external ADP, or activity of the membrane-bound ATP synthase complex results in delta mu H depression with respect to resting state levels. This depression appears to be more pronounced, under strictly comparable conditions, when arsenate is used to stimulate ATP synthase activity than when the ornithine-citrulline conversion reaction is used for the same purpose.
 ...
PMID:Studies on the relationship between ATP synthesis and transport and the proton electrochemical gradient in rat liver mitochondria. 621 98

Blood sampled from the coronary sinus was compared with blood collected simultaneously from the superior caval vein in 50 men with angiographically proven coronary heart disease. Primary, ADP-induced aggregation in coronary sinus blood was reduced by 14 per cent, collagen-induced aggregation by 10 and platelet retention by 16 to 30 per cent as compared with blood from the caval vein. The plasma levels of beta-thromboglobulin, platelet counts and number of circulating platelet aggregates were similar in parallel samples. The reduced platelet function in coronary sinus blood hardly reflects refractoriness after previous platelet stimulation, since no release or irreversible aggregation was induced. A reduced function might be the effect of direct depression induced in the coronary circulation. Most surprisingly, a selective thromboxane synthetase inhibitor (Dazoxiben) and acetylsalicylic acid normalized platelet aggregation but did not affect the low platelet retention response in coronary sinus blood. Thus, the reduced platelet function in coronary sinus blood is not only mediated via prostaglandins.
 ...
PMID:Platelet function in blood from the coronary sinus in patients with arteriosclerotic heart disease. 622 29

The postsynaptic potential (PSP) was recorded from thin slices of the olfactory cortex of the guinea pig. Application of adenosine and adenine nucleotides such as 5'-ATP, 5'-ADP and 5'-AMP in the incubation medium, depressed the amplitude of the PSP without altering the presynaptic fiber potential. The other purine and pyrimidine derivatives had no inhibitory effect. The inhibitory action of adenosine and adenine nucleotides on the PSP were manifest at concentrations of 5 microM-1 mM. Adenosine, 5'-ATP, 5'-ADP and 5'-AMP were equipotent in evoking depression of PSPs. Inhibition occurred within 10-20 sec after administration of the agents and the depressant effect disappeared rapidly after the removal of the compounds from the medium. Theophylline reversed and prevented the inhibition produced by adenosine and adenine nucleotides. To test the structure-activity relationships of these compounds, adenosine analogs and adenine nucleotide derivatives were applied to the medium. The 6-aminopurine riboside (adenosine radical) was found to be essential for inhibitory action on the PSP. Among adenosine analogs, the presence of at least one hydrogen atom in the amino group at the 6-position of the purine, and the OH group at the 2'-position of the ribose was essential for inhibitory activity.
 ...
PMID:Inhibitory action of adenosine and adenosine analogs on neurotransmission in the olfactory cortex slice of guinea pig - structure-activity relationships. 624 64

ATP, ADP, AMP, IMP, adenosine, inosine and cyclic AMP were measured in slices of the rat hippocampus maintained in vitro. Immediately following cutting ATP was low (3.5 +/- 0.6 nmol/mg protein) and AMP high (8.6 +/- 0.9 nmol/mg), giving an energy charge of only 0.34 +/- 0.02. Over the next 90 min the energy charge gradually normalized (to 0.92 +/- 0.01), partly due to conversion of AMP to ATP, but mainly to breakdown to adenosine and other purines which were recovered in the incubation medium. Total purine content decreased from approximately 18 to 10 nmol/mg protein in the first hour following cutting. In slices from old rats the energy charge was lower 60 min following preparation than in younger rats, while cyclic AMP and adenosine levels were higher. The adenosine antagonist 8-phenyl-theophylline tended to enhance the recovery of responsiveness after preparation of the slices. Stimulation of excitatory afferent fibers at a frequency of 10 Hz for 5 min did not significantly alter the purine levels in brain slices, while hypoxia decreased the energy charge significantly and tended to increase adenosine levels. These changes occurred somewhat later than the fall in electrophysiological responsiveness. 8-Phenyl-theophylline was able to delay somewhat the decline in the amplitude of synaptic responses under hypoxic conditions. It is concluded that the viable part of the hippocampal slice, which accounts for about half of the tissue, has levels of adenine nucleotides and adenosine which are similar to those found in the intact rat brain. The return of electrophysiological function following slice preparation is paralleled by a normalization of the energy charge, the adenosine level and the concentration of cyclic AMP. The absence of electrophysiological activity following cutting, and the decreases in such responses following either prolonged afferent stimulation or hypoxia may be related to changes in purine concentration in the slice. Although adenosine accumulating in the slice may contribute to the depression of electrophysiological responses it is probably not the major factor responsible for the reduction in synaptic responsiveness.
 ...
PMID:Levels of adenosine and adenine nucleotides in slices of rat hippocampus. 632 48

By Northern blot hybridization analysis, we demonstrated that the steady-state levels of mRNAs specifying the alpha subunit of ATPase, the beta subunit of ATPase, and the ATP/ADP translocator are all reduced in cells grown in glucose-rich medium. The extent to which glucose represses the levels of alpha, beta, and translocator mRNAs varies from strain to strain, from 2.5- to 7-fold. Furthermore, by hybridization experiments with an excess of DNA, we showed that glucose represses the rates of synthesis of these mRNAs. The kinetics of repression and depression of transcription were also studied. Finally, a mutant was characterized which appears to be defective in depression of transcription of the genes encoding the alpha and beta ATPase subunits as well as the ATP/ADP translocator.
 ...
PMID:Glucose represses transcription of Saccharomyces cerevisiae nuclear genes that encode mitochondrial components. 632 77

[(5Z,13E,9 alpha,11 alpha,15S)-2,3,4-Trinor - 1,5 - inter-m - phenylene - 6,9 - epoxy - 11,5 - dihydroxy - 15 - cyclohexyl - 16,17,18,19,20-pentanor]- prosta-5,13-dienoic acid (sodium salt) (CG 4203) is a new stable epoprostenol (prostacyclin) analogue with a relative platelet antiaggregatory potency of 0.46 (ADP aggregation in vitro) and a hypotensive potency of 0.14 (anaesthetized rat i.v.) as compared to epoprostenol. In isolated perfused rat hearts, CG 4203 (4.64 X 10(-9) mol/l) significantly attenuated arrhythmias and loss of left ventricular creatine kinase (CK) activity observed in control hearts after 30 min perfusion with hypoxic and 30 min reperfusion with oxygenated Krebs-Ringer solution. In anaesthetized rats, CG 4203 (1.0 microgram X kg-1 X min-1 i.v.) significantly reduced incidence of ventricular fibrillation and increase in plasma CK activity after ligation of the left coronary artery. Infusion of 1.0 and 2.15 micrograms X kg-1 X min-1 CG 4203 i.v. in anaesthetized rats dose-dependently inhibited electrocardiographic changes, i.e. ST depression observed after i.v. injection of 1.0 IU X kg-1 vasopressin. In rat models of sustained myocardial hypoxia, myocardial infarction, and transient cardiac ischemia, CG 4203 thus exerts cardioprotective effects which, depending on the model considered, may be ascribed to either its vasodilatory, coronary dilatory, antiaggregatory or epoprostenol-like cytoprotective activity.
 ...
PMID:Cardioprotective action of the new stable epoprostenol analogue CG 4203 in rat models of cardiac hypoxia and ischemia. 644 79

Platelet-rich plasma was incubated with mithramycin in vitro. This diminished platelet aggregation by ADP and adrenaline, but did not interfere with collagen-induced aggregation. Platelet factor 4 release was diminished by ADP and delayed when induced by adrenaline but normal when induced by collagen. Platelet factor 3 availability was not significantly impaired. Reptilase clot retraction was diminished when induced by ADP but normal when induced by collagen. Uptake of 14C-serotonin and 14C-adenine was slightly inhibited. There was no depression in platelet adhesion or release of serum aggregating activity.
 ...
PMID:Influence of mithramycin on some platelet functions in vitro. 644 52

A method for monitoring ADP-induced thromboembolism in mice by means of the measurement of respiratory rate and depth was studied. The measurement were accurately carried out with a new method devised by us. In mice intravenously injected with 5-40 mg ADP/kg, it was found that the respiratory rate decreased transiently and dose-responsively, and that the platelet count also decreased transiently. On the other hand, no decrease in respiratory rate after administration of ADP was observed in neuraminidase-pretreated mice, in which the platelet count was significantly reduced. In the histological examination, platelet thrombi formed in the pulmonary vessels were observed 10 sec after administration of 10 and 40 mg/kg of ADP in mice which had not been treated with neuraminidase. The extent of thromboembolism at the dose of 40 mg/kg showed a tendency to be more marked than that at 10 mg/kg. Pretreatment with 300 mg dipyridamole/kg p.o. prevented the respiratory depression at 40 mg ADP/kg. However, with 10 mg dimorpholamine/kg i.v. or 30 mg warfarin/kg p.o., no preventive effect was observed. Therefore, it was concluded that it is possible to monitor ADP-induced thromboembolism in mice by means of the accurate measurement of the respiratory rate and depth.
 ...
PMID:A method for monitoring ADP-induced thromboembolism in mice. 646 62

Male weanling rats were made copper deficient with a purified diet containing all known essential dietary nutrients except copper. Copper deficiency was verified by indirect (anemia, growth retardation, hypercholesterolemia, gross pathology, and abnormal electrocardiograms) and direct (tissue copper analysis) criteria. His bundle electrographic and electrocardiographic changes detected in the copper-deficient group consisted most notably of depressed His-Purkinje system conductivity and S-T segment depression. Phosphorus-31 nuclear magnetic resonance spectroscopic analysis of cardiac, renal, and hepatic tissue perchloric acid extracts revealed significant metabolic changes associated with the dietary copper deficiency, including a generalized marked decrease in ATP and phosphocreatine levels and a corresponding increase in inorganic orthophosphate and ADP levels in the various tissues. Tissue-specific changes consisting of elevated ribose 5-phosphate (heart), phosphocholine (heart), and inosine monophosphate (kidney) and decreased glycerol 3-phosphorylethanolamine (liver) and glycerol 3-phosphorylcholine (liver) levels were detected in copper-deficient rats. Microscopic examination of heart tissue from copper-deficient rats revealed extensive disruption of mitochondrial fine structure, including fragmentation of cristae and inner and outer mitochondrial membranes, which resulted in pronounced vacuolization throughout the tissue. Although the physiological and metabolic disturbances manifested in hearts from copper-deficient animals generally mimic myocardial responses to chronic ischemia, the observed changes are interpreted in a broader context to represent the appearance of a copper-dependent cardiomyopathy.
 ...
PMID:Physiological and metabolic characterization of a cardiomyopathy induced by chronic copper deficiency. 663 5


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>