ATP released together with acetylcholine as the mediator of neuromuscular depression at frog motor nerve endings.
ATP released together with acetylcholine as the mediator of neuromuscular depression at frog motor nerve endings.
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ATP 与乙酰胆碱一起释放，作为青蛙运动神经末梢神经肌肉抑制的介质。
DOI：
10.1113/jphysiol.1994.sp020176
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Silinsky,EM
中科院分区：
文献类型：
--
作者：
Redman,RS;Silinsky,EM
1.突触前刺激释放的ATP水解为腺苷并介导连接前神经肌肉抑制的假设在脊椎动物神经肌肉接头进行了测试。使用蛙皮心神经肌肉制备物进行诱发乙酰胆碱（ACh）释放和运动神经末梢神经周离子电流的电生理记录。使用筒箭毒碱或α-银环蛇毒素来阻断肌肉收缩。2.无论是α，β-亚甲基ADP（抑制外5 '核苷酸酶，从而防止ATP降解为腺苷）或选择性腺苷受体拮抗剂（8-环戊基烷基黄嘌呤）阻止外源性ATP对ACh释放的抑制作用，以响应低频神经刺激。这些结果证实了早期的研究结果，ATP必须水解为腺苷，以抑制ACh的释放。3.α，β-亚甲基ADP的存在完全防止了对重复高频神经刺激（0.5 - 1 Hz）的神经肌肉抑制。在ACh释放维持良好的条件下（低频刺激，0.05 Hz），α，β-亚甲基ADP对ACh分泌无影响。4.选择性腺苷受体拮抗剂完全消除了重复高频神经刺激（1.0 Hz）产生的神经肌肉抑制，但对低频刺激（0.05 Hz）下的ACh释放没有影响。5.外源性腺苷脱氨酶（5 i.u. ml-1），其将腺苷降解为其无活性的核苷肌苷，也消除了神经肌肉抑制，但在神经刺激频率太低而不能产生连接前抑制时，对ACh释放没有显著影响。6.在最大神经肌肉抑制期间，外源性腺苷或腺苷激动剂2-氯腺苷的作用被阻断。7.运动神经末梢电流的神经束膜记录的钙敏感成分在抑郁期间或应用腺苷受体拮抗剂和腺苷脱氨酶期间没有变化，表明该物种的神经肌肉抑郁与突触前Ca 2+电流的变化无关。8.这些结果表明，在这些实验的条件下，内源性ATP，水解后的腺苷，导致交界前神经肌肉抑制。内源性腺苷的这种抑制作用发生在青蛙中Ca 2+进入位点的远端。
1. The hypothesis that ATP released by presynaptic stimulation is hydrolysed to adenosine and mediates prejunctional neuromuscular depression was tested at vertebrate neuromuscular junctions. Electrophysiological recordings of evoked acetylcholine (ACh) release and perineural ionic currents at motor nerve endings were made using the frog cutaneous pectoris nerve‐muscle preparation. Either tubocurarine or alpha‐bungarotoxin was used to block muscle contractions. 2. Either alpha,beta‐methylene ADP (which inhibits ecto‐5'nucleotidases and thus prevents the degradation of ATP to adenosine) or selective adenosine receptor antagonists (8‐cyclo‐pentyl alkyl xanthines) prevented the inhibitory effects of exogenous ATP on ACh release in response to low‐frequency nerve stimulation. These results confirm earlier findings that ATP must be hydrolysed to adenosine to inhibit ACh release. 3. The presence of alpha,beta‐methylene ADP completely prevented neuromuscular depression in response to repetitive high‐frequency nerve stimulation (0.5‐1 Hz). alpha,beta‐Methylene ADP had no effect on ACh secretion under conditions where ACh release is well maintained (low‐frequency stimulation, 0.05 Hz). 4. Selective adenosine receptor antagonists completely eliminated neuromuscular depression produced by repetitive high‐frequency nerve stimulation (1.0 Hz) but had no effect on ACh release at low frequencies of stimulation (0.05 Hz). 5. Exogenous adenosine deaminase (5 i.u. ml‐1), which degrades adenosine to its inactive nucleoside inosine, also eliminated neuromuscular depression but had no significant effect on ACh release at frequencies of nerve stimulation too low to produce prejunctional depression. 6. During maximal neuromuscular depression, the effects of exogenous adenosine or 2‐chloroadenosine, an adenosine agonist, were occluded. 7. The calcium‐sensitive component of perineurial recordings of motor nerve terminal currents did not change during depression or during application of adenosine receptor antagonists and adenosine deaminase, suggesting that neuromuscular depression in this species was not associated with changes in presynaptic Ca2+ currents. 8. These results suggest that, under the conditions of these experiments, endogenous ATP, after hydrolysis to adenosine, causes prejunctional neuromuscular depression. This inhibitory effect of endogenous adenosine occurs at a site distal to the locus of Ca2+ entry in the frog.