The role of adenosine in alcohol-induced respiratory suppression.
The role of adenosine in alcohol-induced respiratory suppression.
复制标题
腺苷在酒精诱导呼吸抑制中的作用。
DOI：
10.1016/j.neuropharm.2022.109296
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发表时间：
2023-01-01
影响因子：
4.7
通讯作者：
Boison, Detlev
中科院分区：
文献类型：
--
作者：
Purnell, Benton S.;Thompson, Sydney;Bowman, Tenise;Bhasin, Jayant;George, Steven;Rust, Brian;Murugan, Madhuvika;Fedele, Denise;Boison, Detlev
与酒精有关的中毒是急性饮酒过量导致死亡的首要原因。呼吸衰竭是致命性酒精中毒的病理生理学的关键。酒精增加细胞外腺苷的积累。腺苷抑制呼吸。本研究的目的是检验腺苷信号传导有助于酒精诱导的呼吸抑制的假设。在第一个实验中，在注射非选择性腺苷受体拮抗剂咖啡因（40 mg/kg）、酒精（5 g/kg）或酒精和咖啡因的组合后监测小鼠的呼吸。咖啡因减少了酒精引起的呼吸抑制，这表明腺苷有助于酒精对呼吸的影响。第二个实验采用相同的实验设计，但用血脑屏障不渗透性非选择性腺苷受体拮抗剂8-磺苯基茶碱（8-SPT，60 mg/kg）代替咖啡因。8-SPT没有减少酒精诱导的呼吸抑制，这表明腺苷有助于酒精诱导的中枢神经系统呼吸抑制。第三和第四个实验使用与第一个实验相同的实验设计，但使用选择性A1受体拮抗剂DPCPX（1 mg/kg）和选择性A2 A受体拮抗剂istradefylline（3.3 mg/kg）。Istradefylline，但不是DPCPX，减少酒精诱导的呼吸抑制，表明A2 A受体介导的作用。在第五个实验中，在腺苷代谢受损的Adk+/−小鼠中评价了酒精诱导的呼吸抑制。酒精诱导的呼吸抑制在Adk+/−小鼠中加剧。这些发现表明，腺苷能信号有助于酒精诱导的呼吸抑制。提高我们对酒精如何影响呼吸的理解可能会为严重酒精中毒患者带来更好的治疗策略和更好的结果。
Alcohol-related poisoning is the foremost cause of death resulting from excessive acute alcohol consumption. Respiratory failure is crucial to the pathophysiology of fatal alcohol poisoning. Alcohol increases accumulation of extracellular adenosine. Adenosine suppresses breathing. The goal of this investigation was to test the hypothesis that adenosine signaling contributes to alcohol-induced respiratory suppression. In the first experiment, the breathing of mice was monitored following an injection of the non-selective adenosine receptor antagonist caffeine (40 mg/kg), alcohol (5 g/kg), or alcohol and caffeine combined. Caffeine reduced alcohol-induced respiratory suppression suggesting that adenosine contributes to the effects of alcohol on breathing. The second experiment utilized the same experimental design, but with the blood brain barrier impermeant non-selective adenosine receptor antagonist 8-sulfophenyltheophylline (8-SPT, 60 mg/kg) instead of caffeine. 8-SPT did not reduce alcohol-induced respiratory suppression suggesting that adenosine is contributing to alcohol-induced respiratory suppression in the central nervous system. The third and fourth experiments used the same experimental design as the first, but with the selective A1 receptor antagonist DPCPX (1 mg/kg) and the selective A2A receptor antagonist istradefylline (3.3 mg/kg). Istradefylline, but not DPCPX, reduced alcohol-induced respiratory suppression indicating an A2A receptor mediated effect. In the fifth experiment, alcohol-induced respiratory suppression was evaluated in Adk+/− mice which have impaired adenosine metabolism. Alcohol-induced respiratory suppression was exacerbated in Adk+/− mice. These findings indicate that adenosinergic signaling contributes to alcohol-induced respiratory suppression. Improving our understanding of how alcohol affects breathing may lead to better treatment strategies and better outcomes for patients with severe alcohol poisoning.
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影响因子：
4.7
作者：
Falquetto B;Oliveira LM;Takakura AC;Mulkey DK;Moreira TS
通讯作者：
Moreira TS
DOI：
10.1111/j.1742-7843.2004.pto950509.x
发表时间：
2004-12-01
影响因子：
3.1
作者：
Connole, L;Harkin, A;Maginn, M
通讯作者：
Maginn, M
影响因子：
6.1
作者：
DAR, MS;MUSTAFA, SJ;WOOLES, WR
通讯作者：
WOOLES, WR
DOI：
10.1111/j.1365-2125.1995.tb04562.x
发表时间：
1995-10-01
影响因子：
3.4
作者：
AZCONA, O;BARBANOJ, MJ;JANE, F
通讯作者：
JANE, F
影响因子：
3.3
作者：
ELDRIDGE, FL;MILLHORN, DE;KILEY, JP
通讯作者：
KILEY, JP