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

Adenosine is a potent neuromodulator in the CNS, but the mechanisms that regulate adenosine concentrations in the extracellular space remain unclear. The present study demonstrates that increasing the intracellular concentration of adenosine in a single hippocampal CA1 pyramidal neuron selectively inhibits the excitatory postsynaptic potentials in that cell. Loading neurons with high concentrations of adenosine via the whole-cell patch-clamp technique did not affect the GABAA-mediated inhibitory postsynaptic potentials, the membrane resistance, or the holding current, whereas it significantly increased the adenosine receptor-mediated depression of excitatory postsynaptic currents. The effects of adenosine could not be mimicked by an agonist at the intracellular adenosine P-site, but the effects could be antagonized by a charged adenosine receptor antagonist and by adenosine deaminase, demonstrating that the effect was mediated via adenosine acting at extracellular adenosine receptors. The effect of adenosine loading was not blocked by BaCl2 and therefore was not caused by an adenosine-activated postsynaptic potassium conductance. Adenosine loading increased the paired-pulse facilitation ratio, demonstrating that the effect was mediated by presynaptic adenosine receptors. Finally, simultaneous extracellular field recordings demonstrated that the increase in extracellular adenosine was confined to excitatory synaptic inputs to the loaded cell. These data demonstrate that elevating the intracellular concentration of adenosine in a single CA1 pyramidal neuron induces the release of adenosine into the extracellular space in such a way that it selectively inhibits the excitatory inputs to that cell, and the data support the general conclusion that adenosine is a retrograde messenger used by pyramidal neurons to regulate their excitatory input.
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PMID:Modulation of excitatory synaptic transmission by adenosine released from single hippocampal pyramidal neurons. 879 16

The present study was designed to investigate mechanisms of adenosine (ADO)-mediated prolongation of conductivity through the atrioventricular (AV) node during myocardial ischemia. Using the Langendorff preparation of the guinea pig heart, we tested the hypothesis that extracellular potassium concentration elevated due to ischemia could augment ADO effect. Exposure of the heart preparation to either stop-flow or hypoxic Krebs-Henseleit solution (KH) inhibited AV node conductivity observed as an increase in SH interval, and finally resulted in AV block. Superficial potassium concentration ([K+]s), recorded simultaneously increased in response to each stop-flow or hypoxia. Application of 0.1 mM BaCl2 markedly increased the SH interval, yet it did neither protect the heart from hypoxia-evoked AV block nor did it prevent hypoxia-induced [K+]s elevation. Neither did perfusion of the myocardium with modified KH containing 8 mM K+ affect the hypoxic AV block and [K+]s increase. The hypoxic effects were not affected by adenosine A1 agonist N6-cyclopentyl-adenosine (CPA, 30 nM). In the presence of CPA, application of high-K+ KH, where potassium was elevated to the value of hypoxic level, did not affect the SH interval. On the other hand, adenosine deaminase (ADA, 4 U/ml) significantly attenuated the hypoxic AV block. This indicated an involvement of endogenous ADO. Yet, in the presence of both ADA and CPA, the application of the high-K+ KH did not affect the SH interval. We concluded that increased extracellular [K+], elevated due to hypoxia, did not participate in the hypoxia-induced AV block mediated by ADO.
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PMID:On augmentation of adenosine-mediated negative dromotropic effect by K+ released during myocardial ischemia. 1514 72