Sources of adenosine released during neuromuscular transmission in the rat.
Sources of adenosine released during neuromuscular transmission in the rat.
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大鼠神经肌肉传递过程中释放的腺苷来源。
DOI：
10.1113/jphysiol.1991.sp018388
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Smith,DO
中科院分区：
文献类型：
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作者：
Smith,DO
1. 采用生物化学方法测定了大鼠指长伸肌神经刺激时神经肌肉接点积聚的腺嘌呤核苷酸和腺苷水平。来源也通过使用不同的抑制剂来确定。2. ATP和总腺嘌呤核苷酸释放随着刺激频率的增加而增加，这与先前的证据一致，表明ATP释放来自突触前来源。3. 腺苷水平在神经刺激时也增加。然而，当添加d -管curarine （dTC）阻断肌肉激活时，积累减少了46 - 58%。当加入1 mM‐α， β‐甲基腺苷5′‐二磷酸阻断腺嘌呤核苷酸水解为腺苷时，腺苷水平也下降了40‐59%。因此，大约一半的胞外腺苷从活化的肌肉中释放出来，而另一半来源于腺嘌呤核苷酸水解。4. 类似数量的腺嘌呤核苷酸和乙酰胆碱（ACh）在神经刺激过程中积累。腺嘌呤核苷酸和乙酰胆碱水解分别被α、β -甲基腺苷5′-二磷酸和eserine阻断，计算的腺嘌呤核苷酸和乙酰胆碱释放量分别为1.2 × 10（‐16）和1.5 × 10（‐16）mol（刺激脉冲）‐1终板‐1。5. 阻断乙酰胆碱释放的AH5183 （vesamicol）分别使细胞外乙酰胆碱和腺嘌呤核苷酸的积累减少40%和45%。它不影响腺苷释放从激活的肌肉。6. 阻断腺苷受体的茶碱（100 μ m）使ATP积累增加38%；胞外由腺嘌呤核苷酸水解产生的腺苷水平也增加了17%。这些结果与腺苷介导的腺嘌呤核苷酸释放抑制的存在一致。7. 结论是腺嘌呤核苷酸（可能以ATP的形式）和乙酰胆碱共同释放，ATP水解成腺苷的速度相当快。由ATP水解产生的腺苷约占神经刺激过程中积累的细胞外腺苷的一半，而另一半则由底层肌肉直接释放。
1. The levels of adenine nucleotides and adenosine which accumulate in the neuromuscular junction during nerve stimulation of the rat extensor digitorum longus (EDL) muscle were assayed biochemically. The sources were also determined by the use of different inhibitors. 2. ATP and total adenine nucleotide release increased as stimulation frequency increased, consistent with previous evidence indicating ATP release from presynaptic sources. 3. Adenosine levels also increased during nerve stimulation. However, accumulation decreased by 46‐58% when muscle activation was blocked by the addition of d‐tubocurarine (dTC). Adenosine levels also decreased by 40‐59% when adenine nucleotide hydrolysis to adenosine was blocked by the addition of 1 mM‐alpha,beta‐methyladenosine 5'‐diphosphate. Thus, approximately half of the extracellular adenosine is released from activated muscle while the other half is derived from adenine nucleotide hydrolysis. 4. Similar quantities of adenine nucleotide and acetylcholine (ACh) accumulated during nerve stimulation. With adenine nucleotide and ACh hydrolysis blocked by alpha,beta‐methyladenosine 5'‐diphosphate and eserine, respectively, the calculated amounts of adenine nucleotide and ACh released were 1.2 x 10(‐16) and 1.5 x 10(‐16) mol (stimulus impulse)‐1 endplate‐1. 5. AH5183 (vesamicol), which blocks ACh release, reduced extracellular ACh and adenine nucleotide accumulation by 40 and 45%, respectively. It did not affect adenosine release from the activated muscle. 6. Theophylline (100 microM), which blocks adenosine receptors, caused ATP accumulation to increase by 38%; extracellular levels of adenosine derived from adenine nucleotide hydrolysis also increased by 17%. These results are consistent with the presence of adenosine‐mediated inhibition of adenine nucleotide release. 7. It is concluded that adenine nucleotides (presumably in the form of ATP) and ACh are released jointly, and that ATP is hydrolysed fairly rapidly to adenosine. Adenosine resulting from ATP hydrolysis accounts for about half of the extracellular adenosine accumulating during nerve stimulation, while the other half is released directly by the underlying muscle.