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 relationship between energy preservation and the recovery of heart function was studied in globally ischemic hearts which were treated with verapamil. Isolated working rat hearts reperfused after 27 min of ischemia recovered 17.9 +/- 5.11% of pre-ischemic contractile function and had markedly reduced tissue ATP, total adenine nucleotide, and creatine phosphate levels. The ATP/ADP ratio was also decreased in these hearts. When verapamil (2 X 10(-6) M) was present before and during ischemia, but not during reperfusion, the recovery of cardiac function following reperfusion was improved (82.4 +/- 12.1%). When hearts were treated with 0.0, 7.5 X 10(-8) M, 5 X 10(-7) M, or 2 X 10(-6) M verapamil, the recovery of cardiac function was proportional to the concentration of verapamil present and showed a linear relationship with the depression of cardiac function prior to ischemia. The ATP, total adenine nucleotide and creatine phosphate levels were significantly higher in those hearts which were treated with verapamil, but the increase was not proportional to the recovery of cardiac function. It is possible that a critical pool of ATP may correlate with the recovery of verapamil treated hearts, but a large degree of mechanical recovery occurred with significant loss of high energy phosphate stores. Thus, while high energy compounds were preserved, there was not a good correlation between recovery of cardiac function and the preservation of total tissue energy reserves. A portion of the protection afforded by verapamil to globally ischemic hearts may be due to energy preservation, but additional mechanisms may also be involved in the enhanced recovery of contractile function.
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PMID:Protection by verapamil of globally ischemic rat hearts: energy preservation, a partial explanation. 404 46

1. Stimulation of the vagal non-adrenergic inhibitory innervation caused the release of adenosine and inosine into vascular perfusates from the stomachs of guinea-pigs and toads.2. Stimulation of portions of Auerbach's plexus isolated from turkey gizzard caused the release of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP).3. ATP, added to solutions perfused through the toad stomach vasculature, was broken down to adenosine, inosine and adenine.4. Of a series of purine and pyrimidine derivatives tested for inhibitory activity on the guinea-pig isolated taenia coli, ATP and ADP were the most potent.5. ATP caused inhibition of twelve other gut preparations previously shown to contain non-adrenergic inhibitory nerves. The inhibitory action of ATP was not prevented by tetrodotoxin.6. Quinidine antagonized relaxations of the guinea-pig taenia coli caused by catecholamines or adrenergic nerve stimulation. Higher concentrations of quinidine antagonized relaxations caused by ATP or non-adrenergic inhibitory nerve stimulation.7. When tachyphylaxis to ATP had been produced in the rabbit ileum, there was a consistent depression of the responses to non-adrenergic inhibitory nerve stimulation but not of responses to adrenergic nerve stimulation.8. It is suggested that ATP or a related nucleotide is the transmitter substance released by the non-adrenergic inhibitory innervation of the gut.
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PMID:Evidence that adenosine triphosphate or a related nucleotide is the transmitter substance released by non-adrenergic inhibitory nerves in the gut. 2788 76

1. Two-day-old rats were exposed at constant temperature to atmospheres containing air and nitrogen with the air content varied in steps from 100 to 0%. By using this system of graded hypoxia a comparison was made between rates of gluconeogenesis from lactate, serine and aspartate in the whole animal and the concentrations of several liver metabolites. 2. Gluconeogenesis, expressed as the percentage incorporation of labelled isotope into glucose plus glycogen, proceeds linearly for 30min when the animals are incubated in a normal air atmosphere, but is completely suppressed if the atmosphere is 100% nitrogen. 3. Preincubation of animals for between 5 and 30min under an atmosphere containing 19% air results in the attainment of a new steady state with respect to gluconeogenesis and hepatic concentrations of ATP, ADP, AMP, lactate, pyruvate, beta-hydroxybutyrate and acetoacetate. 4. When lactate (100mumol), aspartate (20mumol) or serine (20mumol) was injected, it was shown that the more severe the hypoxia the greater the depression of gluconeogenesis. Under conditions when gluconeogenesis was markedly inhibited there were no changes in the degree of phosphorylation of hepatic adenine nucleotides, but free [NAD(+)]/[NADH] ratios fell in both cytosol and mitochondrial compartments of the liver cell. 5. Measurements of total liver NAD(+) and NADH showed that the concentrations of these nucleotide coenzymes changed less with anoxia, in comparison with the concentration ratio of free coenzymes. 6. Calculations showed that the difference in NAD(+)-NADH redox potentials between mitochondrial and cytosol compartments increased with the severity of hypoxia. 7. From the constancy of the concentrations of adenine nucleotides it is concluded that liver of hypoxic rats can conserve ATP by lowering the rate of ATP utilization for gluconeogenesis. Gluconeogenesis may be regulated in turn by the changes in mitochondrial and cytosol redox state.
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PMID:Regulation of gluconeogenesis during exposure of young rats to hypoxic conditions. 433 87

BM 13.177 (0.1-100 microM) produced a concentration-dependent reduction of the platelet shape change, aggregation and (3H)serotonin release induced by the stable PGH2 analogues U 46619 and U 44069 or exogenous and endogenous arachidonic acid, the latter mobilized by hydrogen peroxide or collagen. BM 13.177 (100 microM) did not inhibit the primary platelet activation by ADP, serotonin, thrombin or collagen in washed platelets or citrated PRP that had been pre-treated with ASA (acetylsalicylic acid). The formation of TXB2 triggered by 100 microM hydrogen peroxide or 10 microM arachidonic acid was not influenced by BM 13.177 (10 microM). In spiral strips of rat and rabbit aorta, BM 13.117 markedly reduced the vasoconstriction triggered by U 46619 and PGF2 alpha. BM 13.177 did not inhibit the K+-or noradrenaline-induced constriction. The concentration/response curves of the U 46619-stimulated platelet shape change and of the vasoconstriction induced by U 46619 and PGF2 alpha were shifted in parallel to the right by BM 13.177, implicating a competitive antagonism. The pAx values were about the same in these models which indicates that BM 13.177 does not differentiate between the thromboxane receptors in human platelets and rabbit aorta. In mice, BM 13.177 prevented in a dose-dependent fashion the sudden death and the symptoms of respiratory depression and shock induced by i.v. injections of U 46619 or arachidonic acid. BM 13.177 did not exert partial agonist activity in the in vitro and in the animal models.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibitory effects of the selective thromboxane receptor antagonist BM 13.177 on platelet aggregation, vasoconstriction and sudden death. 609 35

In the transversely cut rat hippocampus, adenosine caused a dose-dependent increase in the accumulation of [3H]cyclic AMP from [3H]ATP. Adenosine breakdown products were inactive. AMP was somewhat less effective than adenosine, and its effect could be partially, but not completely, abolished by alpha, beta-methylene-ADP and GMP, which inhibited its metabolism by 5'-nucleotidase. The effect of adenosine was unaffected by inhibitors of adenosine deaminase, but enhanced by several inhibitors of adenosine uptake. Some analogues of adenosine, including N6-phenylisopropyladenosine (PIA), 2-chloroadenosine and adenosine 5'-ethylcarboxamide (NECA), were more active than adenosine, whereas others such as 2-deoxyadenosine and 9-(tetrahydro-2-furyl)adenine (SQ 22536) actually inhibited the response. The effect of PIA was highly stereospecific. The action of adenosine was inhibited by several alkylxanthines, the most potent of which was 8-phenyltheophylline. [3H]Cyclohexyladenosine (CHA) bound specifically to cell membranes from the rat hippocampus. The extent of binding was similar to that found in other cortical areas. The relative potency of some adenosine analogues and alkylxanthines to displace labelled CHA was essentially similar to their potency as effectors of the cyclic AMP system. Adenosine contributed to the cyclic AMP-elevating effect of alpha-adrenoceptor-stimulating drugs and several amino acids, but not to that seen with isoprenaline. The cyclic AMP increase seen following depolarization was only partially adenosine-dependent. The present results demonstrate that the rat hippocampus contains adenosine receptors mediating cyclic AMP accumulation and that these receptors have similar characteristics to those mediating pyramidal cell depression. Adenosine-induced cyclic AMP accumulation may be used as a biochemical correlate to electrophysiology and as a convenient parameter to assess the influence of drugs on adenosine mechanisms in the rat hippocampus.
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PMID:Adenosine receptors mediating cyclic AMP production in the rat hippocampus. 612 48

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.
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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.
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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.
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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.
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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.
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PMID:Levels of adenosine and adenine nucleotides in slices of rat hippocampus. 632 48


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