TONIC ADENOSINE A(2A) RECEPTOR ACTIVATION MODULATES NICOTINIC AUTORECEPTOR FUNCTION AT THE RAT NEUROMUSCULAR-JUNCTION
TONIC ADENOSINE A(2A) RECEPTOR ACTIVATION MODULATES NICOTINIC AUTORECEPTOR FUNCTION AT THE RAT NEUROMUSCULAR-JUNCTION
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DOI：
10.1016/0014-2999(94)90793-5
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发表时间：
1994-12-27
影响因子：
5
通讯作者：
RIBEIRO, JA
中科院分区：
文献类型：
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作者：
CORREIADESA, P;RIBEIRO, JA
研究了突触前腺苷受体激活对大鼠膈运动神经末梢电诱发[H-3]乙酰胆碱释放的烟碱自易化的影响。用3，7-二甲基-1-炔丙基黄嘌呤阻断腺苷A（2A）受体（DMPX，10 μ M）大大增强，而腺苷A（1）受体拮抗剂，1，3-二丙基-8-环戊基黄嘌呤（DPCPX，2.5 nM），部分阻止烟碱受体激动剂1，1-二甲基-4-苯基哌嗪鎓的易化作用（DMPP，1 μ M，3分钟），对诱发的[H-3]乙酰胆碱释放。腺苷A（2A）受体激动剂2-[p-（2-carboxyethyl）phenethylamino]-5 '-N-ethylcarboxamideadenosine（CGS 21680 C，3 nM）部分阻断DMPP（1 μ M）的易化作用，而腺苷A（1）受体激动剂R-N-6-phenylisopropyl adenosine（R-PIA，300 nM）则不能。毛喉素（3 μ M）模拟CGS 21680 C引起的衰减;用N-（as-2-苯基环戊基）氮杂环十三烷-2-亚胺盐酸盐（MDL 12，330 A，10 μ M）抑制腺苷酸环化酶显著增强DMPP（1 μ M）的易化作用。长时间暴露于高浓度的DMPP（10 μ M，15分钟）减少诱发氚流出。诱导的[3 H]乙酰胆碱释放后，长期暴露于DMPP的减少增加预处理CGS 21680 C（3 nM）和毛喉素（3 μ M），并取消了与腺苷脱氨酶（0.5 U/ml）灭活内源性腺苷。结论：紧张性腺苷A（2A）受体激活调节烟碱乙酰胆碱自易化。这种作用可能是通过腺苷酸环化酶/环AMP依赖性机制介导的。
The influence of the activation of presynaptic adenosine receptors on nicotinic autofacilitation of electrically evoked [H-3]acetylcholine release from rat phrenic motor nerve terminals was investigated. Blocking the adenosine A(2A) receptor with 3,7-dimethyl-1-propargylxanthine (DMPX, 10 mu M) greatly potentiated, whereas the adenosine A(1) 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 mu M, 3 min), on evoked [H-3]acetylcholine release. The adenosine A(2A) receptor agonist, 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamideadenosine (CGS 21680C, 3 nM), but not the adenosine A(1) receptor agonist, R-N-6-phenylisopropyl adenosine (R-PIA, 300 nM), partially blocked the DMPP (1 mu M) facilitation. Forskolin (3 mu M) 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 mu M) markedly enhanced the facilitatory effect of DMPP (1 mu M). Prolonged exposure to a high concentration of DMPP (10 mu M, 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 mu M), and was abolished by inactivating endogenous adenosine with adenosine deaminase (0.5 U/ml). It is concluded that tonic adenosine A(2A) receptor activation regulates nicotinic acetylcholine autofacilitation. This action is likely to be mediated through an adenylate cyclase/cyclic AMP-dependent mechanism.