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)

The influence of the activation of presynaptic adenosine receptors on nicotinic autofacilitation of electrically evoked [3H]acetylcholine release from rat phrenic motor nerve terminals was investigated. Blocking the adenosine A2A receptor with 3,7-dimethyl-1-propargylxanthine (DMPX, 10 microM) greatly potentiated, whereas the adenosine A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 2.5 nM), partially prevented the facilitatory effect of the nicotinic receptor agonist, 1,1-dimethyl-4-phenylpiperazinium (DMPP, 1 microM, 3 min), on evoked [3H]acetylcholine release. The adenosine A2A receptor agonist, 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamideadeno sine (CGS 21680C, 3 nM), but not the adenosine A1 receptor agonist, R-N6-phenylisopropyl adenosine (R-PIA, 300 nM), partially blocked the DMPP (1 microM) facilitation. Forskolin (3 microM) mimicked the attenuation caused by CGS 21680C; inhibition of adenylate cyclase with N-(as-2-phenylcyclopentyl)azacyclo-tridecan-2-imine hydrochloride (MDL 12,330A, 10 microM) markedly enhanced the facilitatory effect of DMPP (1 microM). Prolonged exposure to a high concentration of DMPP (10 microM, 15 min) decreased evoked tritium outflow. The decrease in evoked [3H]acetylcholine release following prolonged exposure to DMPP was augmented by pretreatment with CGS 21680C (3 nM) and forskolin (3 microM), and was abolished by inactivating endogenous adenosine with adenosine deaminase (0.5 U/ml). It is concluded that tonic adenosine A2A receptor activation regulates nicotinic acetylcholine autofacilitation. This action is likely to be mediated through an adenylate cyclase/cyclic AMP-dependent mechanism.
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PMID:Tonic adenosine A2A receptor activation modulates nicotinic autoreceptor function at the rat neuromuscular junction. 770 35

In addition to the somatodendritic region, myenteric motoneuron terminals are endowed with nicotinic autoreceptors. We aimed at investigating the effect of nicotinic receptor (nAChR) activation on [3H]-acetylcholine ([3H]-ACh) release from longitudinal muscle-myenteric plexus of the rat ileum and to evaluate whether this could be modulated by adenosine, an endogenous neuromodulator typically operating changes in intracellular cyclic AMP. The nAChR agonist, 1,1-dimethyl-4-phenylpiperazinium (DMPP, 1-30 microM, 3 min) increased [3H]-ACh release in a concentration-dependent manner. DMPP (30 microM)-induced [3H]-ACh outflow was attenuated by hexamethonium (0.1-1 mM), tubocurarine (1-5 microM), or by removing external Ca2+ (plus EGTA, 1 mM). In contrast to veratridine (0.2-10 microM)-induced [3H]-ACh release, the DMPP (30 microM)-induced outflow was resistant to tetrodotoxin (1 microM) and cadmium (0.5 mM). Pretreatment with adenosine deaminase (0.5 U/mL) or with the adenosine A(2A)-receptor antagonist, ZM 241385 (50 nM), enhanced nAChR-induced transmitter release. Activation of A(2A) receptors with CGS 21680C (3 nM) reduced the DMPP-induced release of [3H]-ACh. CGS 21680C (3 nM) inhibition was prevented by MDL 12,330A (10 microM, an adenylate cyclase inhibitor) and by H-89 (10 microM, an inhibitor of protein kinase A), but was potentiated by rolipram (300 microM, a phosphodiesterase inhibitor). DMPP-induced transmitter release was decreased by 8-bromo-cyclic AMP (1 mM, a protein kinase A activator), rolipram (300 microM), and forskolin (3 microM, an activator of adenylate cyclase). Both MDL 12,330A (10 microM) and H-89 (10 microM) facilitated DMPP-induced release of [3H]-ACh. The results indicate that nAChR-induced [3H]-ACh release is triggered by the influx of Ca2+, independent of voltage-sensitive calcium channels, presumably directly through nAChRs located on myenteric axon terminals. It was also shown that endogenous adenosine, activating A(2A) receptors coupled to the adenylate cyclase/cyclic AMP transducing system, is tonically downregulating this nAChR-mediated control of [3H]-ACh release.
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PMID:Adenosine activating A(2A)-receptors coupled to adenylate cyclase/cyclic AMP pathway downregulates nicotinic autoreceptor function at the rat myenteric nerve terminals. 1523 6