cAMP production mediated through P2Y11-like receptors in rat striatum due to severe, but not moderate, carbon monoxide poisoning
cAMP production mediated through P2Y11-like receptors in rat striatum due to severe, but not moderate, carbon monoxide poisoning
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DOI：
10.1016/j.tox.2011.07.001
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发表时间：
2011-10-09
期刊：
影响因子：
4.5
通讯作者：
Mukai, Toshiji
中科院分区：
文献类型：
--
作者：
Hara, Shuichi;Mizukami, Hajime;Mukai, Toshiji
我们研究了一氧化碳（CO）中毒的影响，产生的cAMP，细胞内的第二信使，在大鼠纹状体的细胞外cAMP，这是高度相关的细胞内cAMP，通过使用微透析。严重中毒，由于3000 ppm的CO，但不是中度中毒，由于1000 ppm的CO，引起cAMP的增加，这是敏感的电压依赖性Na+通道阻滞剂，河豚毒素，和更深刻的比下可比缺氧引起的5%O-2。这些结果与我们以前关于羟基自由基（（OH）-O-中心点）产生的研究结果相似，表明cAMP与（OH）-O-中心点的产生之间存在密切关系。cAMP的增加被抑制的非选择性嘌呤P2受体拮抗剂，苏拉明。然而，其他非选择性P2受体拮抗剂，吡哆醛磷酸-6-偶氮苯基-2 '，4'-二磺酸和活性蓝2，分别表现出无影响和弱的非显着抑制。P2 Y（11）受体拮抗剂NF 157剂量依赖性地抑制cAMP的增加，尽管大鼠缺乏P2 Y（11）受体。上述结果提示，CO中毒时，Na+内流触发纹状体去极化后，P2 Y（11）样受体介导cAMP产生存在一个阈值，且仅在重度CO中毒时才达到该阈值。该阈值也可能与（OH）-O-中心点的产生有关，有助于CO在脑中的毒性。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
We examined the effect of carbon monoxide (CO) poisoning on the production of cAMP, an intracellular second messenger, in rat striatum in terms of extracellular cAMP, which is highly correlated with intracellular cAMP, by using microdialysis. Severe poisoning due to 3000 ppm CO, but not moderate poisoning due to 1000 ppm CO, caused an increase in cAMP, which was susceptible to a voltage-dependent Na+ channel blocker, tetrodotoxin, and more profound than that under comparable hypoxia caused by 5% O-2. These results were similar to our previous findings on the production of hydroxyl radical ((OH)-O-center dot), suggesting a close relationship between cAMP and (OH)-O-center dot production. The increase in cAMP was suppressed by a non-selective purine P2 receptor antagonist, suramin. However, other non-selective P2 receptor antagonists, pyridoxalphosphate-6-azopheny1-2',4'-disulfonic acid and reactive blue 2, exhibited no effect and weak non-significant suppression, respectively. A P2Y(11) receptor antagonist, NF157, dose-dependently suppressed the increase in cAMP, although rats lack the P2Y(11) receptor. These results suggest that a threshold for cAMP production mediated through P2Y(11)-like receptors following depolarization triggered by Na+ influx exists in rat striatum during CO poisoning, and that the threshold is reached only in cases of severe CO poisoning. It is also likely that the threshold is related to the generation of (OH)-O-center dot, contributing to the toxicity of CO in the brain. (C) 2011 Elsevier Ireland Ltd. All rights reserved.