Adenosine uptake and deamination regulate tonic A2a receptor facilitation of evoked [3H]acetylcholine release from the rat motor nerve terminals

摘要: Abstract The actions of adenosine, adenosine deaminase, the uptake blocker, S -( p -nitrobenzyl)-6-thioinosine, and deaminase inhibitor, erythro-9(2-hydroxy-3-nonyl)adenine, on electrically evoked [ 3 H]acetylcholine release were investigated in rat phrenic nerve-hemidiaphragm preparations. Adenosine (0.25–2.5 U/ml) increased release. -Nitrobenzyl)-6-thioinosine (3–30 μM) erythro-9(2-hydroxy-3-nonyl)adenine (25 nM–50 caused biphasic effects release: at low concentrations -nitrobenzyl)-6-thioinosine (5 (50 nM) decreased release, higher than 10 MM 0.5 μM for facilitated Both -nitrobenzyl)-6-thioinosine-induced inhibition facilitation resulted from extracellular endogenous accumulation, because they blocked after inactivation with (0.5 U/ml). inhibitory both antagonized by A 1 receptor antagonist, 1,3-dipropyl-8cyclopentylxanthine (2.5 nM), whereas blockade 2a receptors PD 115,199 prevented facilitatory (30 erythro-9(2-hydroxy-3nonyl)adenine (50μM). potentiated effect y M), this when applied a concentration (3 that itself was devoid effect, excitatory Exogenously (10–500 had similar to those erythro-9(2-hydroxy-3-nonyl)adenine. reduction pretreatment 1,3-dipropyl-8-cyclopentylxanthine (2.5nM); high (100–500 μM), consistently nM)-sensitive manner. It is concluded deamination are effective removing tonically activates (A ) receptors, regulating /A receptors' activation balance.