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)

A 5-year-old girl with a history of recurrent infection and anaemia has no measurable purine nucleoside phosphorylase (N.P.) activity in her red blood-cells. Her serum-immunoglobulin levels are normal, as are her antibody responses to thymus dependent and independent antigens. However, she has severe lymphopenia, pronounced depression of lymphocyte response to mitogenic and allogeneic cell stimuli, and greatly decreased T-cell rosette formation. Her parents are second cousins; their red cells contain less than half the normal level of N.P. activity. They also share an unusual N.P. isozyme pattern indicative of molecular hybridisation between catalytically active and inactive subunits, which strongly supports the assumption that they are heterozygous and their daughter is homozygous for a "silent" allele at the N.P. gene locus. Inherited deficiency of adenosine deaminase, an enzyme catalysing a reaction only one metabolic step away from that of N.P., is known to cause immunodeficiency. It is therefore very likely that this patient's lack of demonstrable N.P. activity is responsible for her syndrome.
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PMID:Nucleoside-phosphorylase deficiency in a child with severely defective T-cell immunity and normal B-cell immunity. 4 76

The occurrence of severe combined immunodeficiency (SCID) with adenosine deaminase (ADA) deficiency in erythrocytes has been reported in 14 patients. Enzyme deficiency may result in early depression of the lymphatic system. ADA is detectable in different tissues by photometric and electrophoretic methods. The gene locus for ADA has been localised on chromosome 20. Studies on the enzyme defect in different forms of primary immunodeficiencies led to the description of a well defined nosological entity. New aspects can be expected in the fields of pathogenesis, prenatal diagnosis, genetic councelling, and possibly therapeutic trials.
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PMID:[Adenosine deaminase deficiency in primary immunodeficiencies (author's transl)]. 100 69

The effects of 5-amino-4-imidazolecarboxamide riboside (rAICA) on coronary adenosine efflux were examined in blood-free perfused working rat heart preparations subjected to mild (70% O2) and severe hypoxia (45% O2). Under these hypoxic conditions, no significant increase of coronary adenosine effluxes was observed in the presence of 300 microM rAICA alone. However, rAICA-induced augmentation of coronary adenosine efflux during hypoxia was revealed in the presence of an adenosine deaminase inhibitor, erythro-(2-hydroxy-3-nonyl)adenine hydrochloride, indicating that the failure to note the increase in coronary adenosine efflux was due to a rapid deamination of adenosine to inosine. A depression in heart rate during mild and severe hypoxia was significantly exacerbated by rAICA. These effects on heart rate were mediated by adenosine, since they were effectively blocked by 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine, a selective adenosine A1-receptor antagonist. These results suggest that rAICA elevates adenosine efflux during hypoxia.
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PMID:5-Amino-4-imidazolecarboxamide riboside raises adenosine in perfused hypoxic rat heart. 180 58

Neplanocin A is a naturally occurring carbocyclic analog of adenosine which contains a cyclopentene moiety in place of ribose and has demonstrated antitumor and antimicrobial activity. This compound was highly toxic to Chinese hamster ovary (CHO) cells; the approximate minimum inhibitory concentration of neplanocin A for inhibition of clone formation was 0.1 microM. The toxicity of the agent was greatly reduced by prior treatment with adenosine deaminase. [3H]Uridine incorporation into perchloric acid insoluble material in growing cells was inhibited by neplanocin A more dramatically than that of [3H]thymidine or [3H]leucine. Treatment with the drug resulted in a marked depression of ATP pool levels. High pressure liquid chromatographic analysis of cellular nucleotide pools from cells treated with neplanocin A revealed the formation of an apparent drug metabolite (NpcTP) that eluted in the triphosphate region of the chromatographic profile. Treatment of NpcTP with alkaline phosphatase produced a nucleoside with properties similar to neplanocin A. An adenosine-kinase-deficient cell line formed little, if any, NpcTP but demonstrated only slight resistance to the agent. These observations suggest that neplanocin A was efficiently metabolized to the triphosphate level but that this metabolite was responsible for only a fraction of the observed toxicity.
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PMID:Metabolism and action of neplanocin A in Chinese hamster ovary cells. 240 84

Rat hippocampal slices were superfused with low calcium, high magnesium medium. Reductions in flow rate were associated with a marked depression of antidromically elicited afterpotentials with little change in the initial antidromic population spike recorded from CA1 pyramidal neurons. The depression of the afterpotential at the lower flow rates was largely reversed by the adenosine antagonist, theophylline (100 microM), by adenosine deaminase (10 micrograms/ml) and was mimicked by the application of the adenosine reuptake blocker, dipyridamole (100 microM). Since synaptic transmission was blocked, it is concluded that sufficient endogenous adenosine exists in the absence of synaptic function to alter neuronal excitability.
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PMID:Modulation of neuronal excitability by endogenous adenosine in the absence of synaptic transmission. 284 14

The benzodiazepine antagonist Ro 15-1788 has been reported to suppress paired pulse inhibition in the hippocampal slice. It is now shown that the depression of orthodromic synaptic transmission by Ro 15-1788 can be prevented by the adenosine antagonist 8-phenyl-theophylline, or by adenosine deaminase. Since Ro 15-1788 has previously been shown to inhibit adenosine-uptake into rat brain tissue, it is suggested that this property, leading to an accumulation of extracellular adenosine, may underlie its effects on synaptic transmission.
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PMID:The suppression of hippocampal potentials by the benzodiazepine antagonist Ro 15-1788 may be mediated by purines. 301 69

1-Methylisoguanosine, a marine natural product analogue of adenosine, with moderate activity as a benzodiazepine receptor ligand, has previously been shown to have muscle-relaxant and hypothermic activity in mice in vivo. The present experiments showed that the benzodiazepine antagonist Ro15-1788 did not block the in vivo muscle-relaxant and hypothermic effects of 1-methylisoguanosine, suggesting that these particular actions are not due to interactions with benzodiazepine receptors. When applied by microiontophoresis near spontaneously-active neurones or neurones activated by ACh, DL-homocysteate or glutamate in the ventrobasal thalamus of anaesthetized rats, 1-methylisoguanosine had a depressant action; it was similar to adenosine in potency and in its ability to be antagonized by 8-(parasulphophenyl)theophylline. The depression was usually longer lasting than that caused by adenosine, consistent with previous neurochemical data showing it to be resistant to adenosine deaminase and a poor substrate for the uptake system for adenosine in the CNS. These results suggest that the major pharmacological/behavioural actions of 1-methylisoguanosine in vivo are more likely to be caused by an interaction with adenosine receptors, rather than with benzodiazepine sites.
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PMID:1-Methylisoguanosine: interaction with central adenosine receptors and lack of antagonism of its in vivo effects by a benzodiazepine antagonist. 303 18

2-Deoxyglucose uptake (3 min) and 3-O-methylglucose transport (2 s) was measured in rat adipocytes preincubated with 5 microM epinephrine plus adenosine deaminase as described by Green (Green, A. (1983) FEBS Lett. 152, 261-264). 2-Deoxyglucose uptake was about 95% depressed in insulin-treated, but not in 'basal', cells preincubated with epinephrine plus adenosine deaminase for 60 min in broad agreement with Green's report. However, this depression was caused by a decrease in sugar phosphorylation rather than transport. In similarly incubated cells, transport of 3-O-methylglucose, a sugar analogue not phosphorylated in the adipocytes, was not affected by catecholamine plus adenosine deaminase. However, a decrease in transport of about 60% was observed both in the absence and the presence of insulin when the albumin concentration was high enough and the cell concentration low enough to prevent accumulation of free fatty acids in the medium. In addition, the insulin sensitivity with regard to hexose transport was markedly reduced. Transport was approximately doubled in cells incubated with 5 microM epinephrine in the absence of adenosine deaminase. Thus, epinephrine at a high concentration stimulates hexose transport in the absence of adenosine deaminase (presence of adenosine) whereas it inhibits both basal and insulin-stimulated transport in the presence of adenosine deaminase (absence of adenosine).
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PMID:The effect of catecholamines and adenosine deaminase on the glucose transport system in rat adipocytes. 389 Sep 59

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

Adenosine and its analogs depress the firing of neurons in various brain regions. The primary mode of action of adenosine in exerting this action appears to be the depression of calcium entry, thus decreasing presynaptic neurotransmitter release. Adenosine uptake inhibitors and adenosine deaminase inhibitors potentiate the depressant actions of adenosine. Caffeine and theophylline, methylxanthines, antagonize these actions. Adenosine is therefore likely to be released and to exert an ongoing modulation of the neuron excitability in the intact brain. Adenosine uptake by nerve terminals appears to be important in regulating the extracellular concentration of adenosine and thus of adenosine's action. A number of groups of centrally active sedative, anxiolytic and anticonvulsant drugs inhibit adenosine uptake by brain synaptosomal preparations. It is proposed that these agents exert their sedative effects by inhibiting adenosine uptake and thus potentiating depressant actions by locally released adenosine on neuronal activity.
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PMID:Adenosine mediates sedative action of various centrally active drugs. 613 Apr 65


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