Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.5.4.4 (adenosine deaminase)
5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Glutamate inhibits the electrically evoked release of noradrenaline in rabbit brain cortex slices; the inhibition is mediated by adenyl compounds, presumably adenosine. The aim of the present study was to identify the receptors involved in this indirect inhibitory effect of glutamate. Slices of the occipitoparietal cortex were preincubated with [3H]-noradrenaline and then superfused and stimulated by trains of 6 pulses, 100 Hz. 2. The ionotropic glutamate receptor agonists alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AM-PA; 10-100 microM), kainate (10-100 microM) and N-methyl-D-aspartate (NMDA; 30-300 microM) but not the metabotropic glutamate receptor agonist, 1-amino-1,3-cyclopentanedicarboxylate (ACPD; 10-100 microM) reduced the electrically evoked overflow of tritium. 3. The effects of AMPA, kainate and NMDA were attenuated or abolished by the adenosine A1-receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as well as by adenosine A1-receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as well as by adenosine deaminase but not by the alpha 2-adrenoceptor antagonist yohimbine, the gamma-aminobutyric acid (GABA) receptor antagonists, bicuculline and 2-hydroxysaclofen and the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). 4. The NMDA receptor antagonist, 2-amino-5-phosphonopentanoate (AP5) blocked the inhibitory effect of NMDA but not that of AMPA and kainate. The non-NMDA-receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocked the effect of AMPA but not of kainate and NMDA. 5. In addition to decreasing the electrically evoked overflow of tritium, AMPA, kainate and NMDA but not ACPD caused a steep but transient rise of basal tritium efflux. This immediate releasing effect was not significantly changed by DPCPX, adenosine deaminase, yohimbine, bicuculline, 2-hydroxysaclofen and L-NAME (except that L-NAME enhanced the effect of kainate). AP5 and CNQX antagonized the immediate releasing effects in the same way that they antagonized the inhibition by AMPA, kainate and NMDA of the electrically evoked overflow of tritium.6. It is concluded that AMPA, kainate and NMDA, like glutamate, reduce the electrically evoked release of noradrenaline by releasing adenosine or an adenine nucleotide which is then degraded to adenosine. Activation of each of the three ionotropic glutamate receptors, AMPA, kainate and NMDA receptors, but not activation of metabotropic glutamate receptors can initiate this indirect inhibitory effect on the release of noradrenaline (as well as the known noradrenaline releasing effect).
...
PMID:Ionotropic glutamate receptor types leading to adenosine-mediated inhibition of electrically evoked [3H]-noradrenaline release in rabbit brain cortex slices. 750 27

Extracellular adenosine in the striatum of adult male rats was measured by the use of a microdialysis fibre inserted transversely in the striatum. The adenosine concentration in samples of perfusate was determined by HPLC coupled to U.V. detection. The adenosine concentration (corrected for recovery) decreased after implantation of the probe. Two hours later it was 1.83 +/- 0.22 in anaesthetized rats, whereas it was 40% higher in rats in which anaesthesia had been discontinued. Twenty-four hours later the adenosine concentration was 0.124 +/- 0.09 microM; the addition of dipyridamole (100 microM), an adenosine uptake blocker, to the perfusate resulted in a 76% increase in adenosine concentration in the effluent, whereas addition of the adenosine deaminase inhibitor erythro-2-(hydroxy-3-nonyl) adenine (100 microM) caused a 260% increase. The addition of tetrodotoxin (1 microM) was followed by a decrease in basal adenosine concentration and a partial inhibition of the increase in adenosine evoked by K+ depolarization. The increase induced by high K+ was markedly inhibited by the NMDA receptor antagonist D(-)-amino-7-phosphoeptanoic acid (1 mM, D-AP7). These findings indicate that the extracellular adenosine level is influenced by neuronal activity, and that under strong depolarizing conditions the increase in adenosine level involves NMDA receptor activation.
...
PMID:Effect of K+ depolarization, tetrodotoxin, and NMDA receptor inhibition on extracellular adenosine levels in rat striatum. 847 61

Activation of ionotropic but not metabotropic glutamate receptors causes an indirect inhibition of the release of noradrenaline in slices of rabbit brain cortex. The inhibition is mediated by adenosine which activates presynaptic adenosine A1-receptors. The present study characterizes the ionotropic receptor types through which glutamate itself produces this indirect inhibition. Rabbit brain cortex slices were preincubated with [3H]-noradrenaline, superfused with medium containing desipramine (1 microM) and stimulated electrically by trains of 6 pulses at 100 Hz. Glutamate (100-3000 micro M) reduced the electrically evoked overflow of tritium by up to 58%. The effect did not differ 20 min and 60 min after addition of glutamate. Adenosine deaminase (1 U ml-1) as well as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 30 microM) and D-gamma-glutamylamino-methanesulfonate (GAMS; 30 micro M), both of which block kainate receptors, attenuated the glutamate-induced inhibition. The NMDA receptor antagonist 2-amino-5-phosphonopentanoate (AP5; 100 micro M) and the AMPA receptor antagonist 6-nitro-7-sulfamoylbenzo(f)-quinoxaline-2,3-dione (NBQX; 30 micro M) did not change the effect of glutamate. Given alone, CNQX and GAMS, but not AP5 and NBQX, slightly increased the evoked overflow of tritium; the increases were abolished in the presence of adenosine deaminase. The results indicate that activation of kainate but not NMDA and AMPA receptors is involved in the indirect, adenosine-mediated inhibition by exogenous glutamate of the release of noradrenaline in rabbit brain cortex slices. Moreover, as shown by the increase caused by CNQX and GAMS, endogenous excitatory amino acids inhibit the release of noradrenaline through the kainate receptor-adenosine mechanism and thus contribute to the purinergic inhibitory control of noradrenaline release in the brain.
...
PMID:Kainate receptors are involved in the glutamate-induced indirect, purinergic inhibition of [3H]-noradrenaline release in rabbit brain cortex. 875 Sep 16

Unilateral microinjection of N-methyl-D-aspartate (NMDA) into striatum of rats subsequently killed by high-energy focused microwave irradiation significantly increased in vivo levels of endogenous adenosine. At a dose of 25 nmol NMDA, levels of adenosine in injected striata were 263% of levels in uninjected contralateral striata. An inhibitor of adenosine deaminase (deoxycoformycin, DCF) in combination with an inhibitor of adenosine transport (dilazep, DLZP) at a dose that did not affect levels of endogenous adenosine, potentiated NMDA-induced increases in adenosine levels to 426% of contralateral striata. In the presence of DCF and DLZP, NMDA dose-dependently increased levels of adenosine (% of contralateral striatum) from 166% at 10 nmol to 622% at 100 nmol. NMDA-induced increases in levels of endogenous adenosine were completely blocked by prior administration of the NMDA receptor antagonist MK 801 (dizocilpine). Inhibitors of adenosine metabolism and transport may provide therapeutic benefit by potentiating excitatory amino acid-induced increases in levels of endogenous adenosine in vivo.
...
PMID:Enhancement of NMDA-induced increases in levels of endogenous adenosine by adenosine deaminase and adenosine transport inhibition in rat striatum. 884 98

We describe how endogenous adenosine can prevent the induction of homosynaptic long-term depression (LTD) in the CA1 region of slices of adult rat hippocampus. Neither of two consecutive periods of prolonged low frequency stimulation (LFS; 1 Hz, 900 stimuli) of the Schaffer collateral-commissural fibres resulted in the induction of LTD in the CA1 region of hippocampal slices from adult (8-30 week) animals. However, in the presence of adenosine deaminase or the selective adenosine A1 receptor antagonist, 1,3-dipropyl-8-cyclopentyl-xanthine (DPCPX), LTD was induced by each of the first and second of two periods of LFS. The first period of LFS did not, but the second period of LFS did, induce LTD in the presence of DPCPX and the NMDA receptor antagonist, D-2-amino-5-phosphonopentanoate (AP5). The present results show that A1 receptor activation by endogenous adenosine can prevent the induction of LTD in the adult hippocampus.
...
PMID:A role for adenosine in the regulation of long-term depression in the adult rat hippocampus in vitro. 914 2

Activation of glutamate receptors triggers the release of adenosine, which exerts important inhibitory actions in the brain. Evoked adenosine release is potentiated when either adenosine kinase or adenosine deaminase are inhibited. We studied the effects of concurrent inhibition of adenosine kinase and adenosine deaminase on N-methyl-D-aspartate (NMDA)-evoked formation of extracellular adenosine in slices of rat parietal cortex, to determine if combinations of inhibitors of adenosine kinase and adenosine deaminase can produce supra-additive potentiation of this adenosine formation. Combinations of low concentrations of the adenosine kinase inhibitors 5'-amino-5'-deoxyadenosine (0.2 microM) or 5'-iodotubercidin (0.01 microM) with a low concentration of the adenosine deaminase inhibitor 2'-deoxycoformycin (0.2 microM) produced additive potentiations of NMDA-evoked adenosine release from slices of rat parietal cortex. However, combinations of low concentrations of 5'-amino-5'-deoxyadenosine (0.2 microM) or 5'-iodotubercidin (0.01 microM) with a maximal concentration of 2'-deoxycoformycin (200 microM) produced supra-additive potentiation of NMDA-evoked adenosine release. These findings suggest that such combinations of adenosine kinase inhibitors with adenosine deaminase inhibitors may provide useful strategies for developing therapies to treat disorders associated with excessive NMDA receptor activation, such as seizures, ischemic damage and neurodegenerative diseases.
...
PMID:Co-administration of adenosine kinase and deaminase inhibitors produces supra-additive potentiation of N-methyl-D-aspartate-evoked adenosine formation in cortex. 960 Jun 45

Superfusion of rat hippocampal slices with ATP induces a form of facilitation that has been poorly characterised. The present study has confirmed that at low concentrations of ATP (10 microM or less), an initial depression of evoked potential size is followed by a rebound facilitation which is not reproduced by alphabeta-methyleneATP, betagamma-methyleneATP, or the dinucleotide P1,P6-diadenosine hexaphosphate. The post-ATP facilitation could be prevented by the adenosine A1 receptor antagonists 8-phenyltheophylline or 1,3-dipropyl-8-cyclopentyltheophylline (50 nM), or superfusion of adenosine deaminase. The adenosine A2A receptor antagonist 8-(chlorostyryl)-caffeine did not affect the inhibition but prevented the post-ATP facilitation. The NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid prevented the establishment of post-ATP facilitation. The post-ATP facilitation was also blocked by suramin at a concentration (50 microM) that does not block glutamate receptors. Suramin prevented the induction but not the maintenance phase of the post-ATP facilitation. The repeated induction of post-ATP facilitation by bursts of electrical stimulation designed to saturate the normal mechanisms of long-term potentiation prevented the induction of post-ATP facilitation. However, repeated applications of ATP to achieve saturation of its receptor did not prevent the subsequent induction of electrically evoked long-term potentiation. It is concluded that ATP can induce a form of synaptic facilitation which resembles only partially that induced by electrical stimulation and which may require the simultaneous activation of P1 and P2 receptors.
...
PMID:Characterisation of ATP-induced facilitation of transmission in rat hippocampus. 1110 29

Stimulation of N-methyl-D-aspartate (NMDA) receptors on neurons activates both cAMP and cGMP signaling pathways. Experiments were carried out to determine which phosphodiesterase (PDE) families are involved in the hydrolysis of the cyclic nucleotides formed via this mechanism, using primary neuronal cultures prepared from rat cerebral cortex and hippocampus. The nonselective PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX) potentiated the ability of NMDA to increase cAMP and cGMP. However, among the family-selective inhibitors, only the PDE4 inhibitor rolipram enhanced the ability of NMDA to increase cAMP in the neurons. In contrast, only the PDE2 inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) enhanced the ability of NMDA to increase cGMP. Neither adenosine nor an adenosine deaminase inhibitor mimicked the effect of EHNA; this suggests that EHNA's inhibition of PDE2, not its effects on adenosine metabolism, mediates its effects on NMDA-stimulated cGMP concentrations. The PDE inhibitor-augmented effects of NMDA on cAMP and cGMP formation were antagonized by 5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine maleate (MK-801), verifying NMDA receptor mediation. In contrast, only NMDA-mediated cGMP formation was affected by altering either nitric oxide signaling or guanylyl cyclase; this suggests that NMDA-induced changes in cAMP are not secondary to altered cGMP concentrations. Overall, the present findings indicate that cAMP and cGMP formed in neurons as a result of NMDA receptor stimulation are hydrolyzed by PDE4 and PDE2, respectively. Selective inhibitors of the two PDE families will differentially affect the functional consequences of activation of these two signaling pathways by NMDA receptor stimulation.
...
PMID:Hydrolysis of N-methyl-D-aspartate receptor-stimulated cAMP and cGMP by PDE4 and PDE2 phosphodiesterases in primary neuronal cultures of rat cerebral cortex and hippocampus. 1206 24

MK-801 was shown to be one of the most neurotoxic non-competitive NMDA receptor antagonists. It is known that repeated injection of MK-801 was proposed in an animal model in psychosis. The aims of this study are to investigate the contributing effect of oxidative stress in MK-801-induced experimental psychosis model, and to show that prevention of oxidative stress may improve prognosis. Furthermore, there is evidence that oxygen free radicals play an important role in the pathophysiology of schizophrenia. In this study, Wistar Albino rats were divided into three groups: 1st group: Control, 2nd group: MK-801, 3rd group: MK-801+CAPE (Caffeic acid phenethyl ester) group. MK-801 was given intraperitoneally at the dose of 0.5 mg/kg/day for 5 days. CAPE was given to the treatment group while exposed to MK-801. In control group, saline was given intraperitoneally at the same time. After 7 days, rats were killed by decapitation. Prefrontal cortex (PFC) of rats was removed for biochemical and histological analyses. As a result, malondialdehyde (MDA), protein carbonyl (PC), nitric oxide (NO) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO) and adenosine deaminase (AD) enzyme activities were found to be increased significantly in prefrontal cortex (PFC) of MK-801 group (p<0.0001) compared to control group. In CAPE treated rats, prefrontal tissue MDA, PC, NO levels and, GSH-Px, XO, AD enzyme activities were significantly decreased when compared to MK-801 groups (p<0.0001) whereas catalase (CAT) enzyme activity was not changed. Moreover, in the light of microscopic examination of MK-801 groups, a great number of apoptotic cells were observed. CAPE treatment decreased the apoptotic cell count in PFC. The results of this study showed that MK-801-induced neurotoxicity caused oxidative stress in PFC of rats. This experimental study may also provide some evidences for the new treatment strategies with antioxidants in schizophrenia.
...
PMID:Oxidative stress in prefrontal cortex of rat exposed to MK-801 and protective effects of CAPE. 1737 54

---