Fine-tuning modulation of myenteric motoneurons by endogenous adenosine: on the role of secreted adenosine deaminase.

摘要: Abstract Besides the well-characterized inhibitory effect of adenosine in gastrointestinal tract mediated by A1 receptors, we recently demonstrated that endogenously generated facilitates [3H]acetylcholine release from myenteric neurons through preferential activation prejunctional A2A receptors. The co-existence both receptor subtypes on cholinergic prompted question how does discriminate between these receptors to regulate synaptic transmission longitudinal muscle-myenteric plexus (LM-MP) rat ileum. Electrical stimulation LM-MP increased outflow adenosine, inosine and hypoxanthine. Myenteric seem be main source endogenous since blockade action potentials with tetrodotoxin (1 μM) or omission Ca2+ (plus EGTA, 1 mM) buffer essentially abolished nucleosides release, while remained unchanged when smooth muscle contractions were prevented nifedipine (1 μM). Inhibition ecto-5′-nucleotidase concanavalin A (0.1 mg ml− 1) produced only a moderate decrease (∼ 25%) accumulation LM-MP, indicating extracellular catabolism released ATP might not major nucleoside. Data using acetylcholinesterase inhibitor, physiostigmine (10 μM), several subtype-specific muscarinic antagonists, 4-DAMP (100 nM), AF-DX 116 (10 μM) toxin-7 (1 nM), suggest motoneurons are endowed M3 autoreceptors facilitating adenosine. Surprisingly, bath samples collected after stimulating exhibited relatively high deaminase (ADA) activity (0.60 ± 0.07 U ml− 1), which parallel its deamination products. Our findings keeping hypothesis ADA secretion, along less-efficient dipyridamole-sensitive nucleoside transport system, may restrict actions region channelling facilitatory activation. Such local environment also limit diffusion exogenously added towards active zones, as showed this constrain overcome inhibiting erythro-9(2-hydroxy-3-nonyl) adenine (50 μM).