Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Field EPSP slope and population spike (PS) amplitude were measured in the CA1 pyramidal cell region after double-pulse stimulation of the striatum radiatum in hippocampal slices of guinea-pig. Iontophoresis of adenosine reduced the EPSP slope to 77.9 +/- 5.0% (mean +/- S.E.M.) and PS amplitude to 32.9 +/- 9.7% of the control values. Recovery was 98.7 +/- 3% for the EPSP and 82.9 +/- 7.0% for the PS 1.5 min after iontophoresis was stopped. In the presence of soluflazine 10(-6) M the effects of adenosine iontophoresis on the PS amplitude were significantly increased and the recovery of the EPSP and PS was significantly delayed. Soluflazine perfusion alone gradually decreased EPSP slope and PS amplitude as with adenosine. The reductions in EPSP slope and PS amplitude produced by soluflazine were antagonized by adenosine deaminase. An increase in EPSP slope and PS amplitude was seen when adenosine deaminase was given first. This increase was not reduced by exposure to soluflazine. These results are compatible with the hypothesis that soluflazine acts as a nucleoside transport inhibitor in the CNS, where it may increase the extracellular concentration of adenosine.
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PMID:The nucleoside-transport inhibitor soluflazine (R 64 719) increases the effects of adenosine in the guinea-pig hippocampal slice and is antagonized by adenosine deaminase. 342 53

Adenosine is a potent inhibitory modulator of synaptic transmission in the CNS, but its role in normal physiological function is unclear. In the present experiments, we have found electrophysiological evidence for activity-dependent release of adenosine from hippocampal slices evoked by physiologically relevant stimulation, and have demonstrated that this adenosine modifies synaptic activity in this brain region. When two independent excitatory pathways to the CA1 pyramidal neurons are used to evoke field EPSP responses, prior activation of one pathway will inhibit the EPSP evoked via the other input. This inhibition can be antagonized by the nonselective adenosine receptor antagonist theophylline, and by the selective A1 receptor antagonist 8-cyclopentyltheophylline, suggesting that the inhibitory response is due to the release of endogenous adenosine that activates presynaptic release-modulating A1 receptors. This inhibition can be observed following a single stimulus to the conditioning pathway, although it is more pronounced when a train of conditioning pulses is used, and is maximal following a train of 16-32 stimuli (at 100 Hz). When a train of four conditioning pulses is used, the inhibition appears with a latency of approximately 50 msec, peaks approximately 200-250 msec following the conditioning train, and recovers to baseline between 1 and 2 sec. Further evidence that this inhibition of excitatory transmission is mediated via adenosine is provided by the observation that superfusion with dipyridamole (an adenosine uptake inhibitor), and the adenosine deaminase inhibitor erythro-(2-hydroxy-3-nonyl)adenine, enhanced both the duration and amplitude of the inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activity-dependent release of endogenous adenosine modulates synaptic responses in the rat hippocampus. 839 82

The excitatory action of brain-derived neurotrophic factor (BDNF) on synaptic transmission is triggered by adenosine A2A receptor activation. Since high-frequency neuronal firing, such as that inducing long-term potentiation (LTP), favours both A2A receptor activation and BDNF effects on transmission, we now evaluated the influence of adenosine on the facilitatory action of BDNF upon CA1 hippocampal LTP. theta-Burst stimulation of the pyramidal inputs induced a significant and persistent increase in field EPSP slopes, and this potentiation was augmented in the presence of BDNF (20 ng/ml), an action prevented by the inhibitor of Trk receptor autophosphorylation, K252a (200 nM). Removal of endogenous extracellular adenosine with adenosine deaminase (ADA, 1 U/ml), as well as the antagonism of adenosine A2A receptors with SCH58261 (100 nM), prevented the excitatory action of BDNF upon LTP. In an adenosine depleted background (with ADA), activation of adenosine A2A receptors (with 10nM CGS21680) restored the facilitatory effect of BDNF on LTP; this was fully prevented by the protein kinase A inhibitor, H-89 (1 microM) and mimicked by the adenylate cyclase activator, forskolin (10 microM). In similar experiments, activation of adenosine inhibitory A1 receptors (with 5 nM CPA) did not affect the facilitatory effect of BDNF. In conclusion, the facilitatory action of BDNF upon hippocampal LTP is critically dependent on the presence of extracellular adenosine and A2A receptor activation through a cAMP/PKA-dependent mechanism. Since extracellular adenosine accumulates upon high-frequency neuronal firing, the present results reveal a key process to allow the influence of BDNF upon synaptic plasticity.
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PMID:Enhancement of long-term potentiation by brain-derived neurotrophic factor requires adenosine A2A receptor activation by endogenous adenosine. 1838 19