The interaction of adenosine and dopamine in modulating the consequences of central nervous system oxygen toxicity.

IF 3.3 3区 医学 Q1 PHYSIOLOGY Journal of applied physiology Pub Date : 2024-11-27 DOI:10.1152/japplphysiol.00500.2024
Benming You, Guorong Shi, Yanan Zhang, Xiang Fu, Qian Li, Yu Wang, Guoyang Huang, Yiqun Fang, Runping Li
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Abstract

Hyperbaric oxygen (HBO) refers to pure oxygen with a pressure greater than 1 atmospheres absolute (ATA), and when the pressure is too high, it can cause convulsive attacks. Adenosine and dopamine have been shown to be closely associated with HBO induced convulsion seizures, and their receptors exhibited a coexisting relationship of mutual antagonism on the membrane of nerve cells. We explored the influence of adenosine and dopamine interplay on the occurrence of oxygen convulsion. Rats were individually exposed to HBO of 6 ATA and treated with adenosine, dopamine, and their receptor modulators separately and jointly, with the latency of convulsion onset recorded. Additionally, after administering adenosine to rats and exposing them to HBO for 30 min, the content of dopamine and its metabolites, as well as the activity of enzymes related to their metabolism, were measured. The results revealed that dopamine was effective in resisting convulsion (> 60 min vs 32.53±5.31 min, P=0.000), and low-dose adenosine partially counteracted its effect (> 60 min vs 28.18±6.24 min, P=0.002). The combined use of adenosine A1 and dopamine D1 receptor modulators significantly impacted the incidence of convulsion. The activation or inhibition of A2A receptor had a particularly significant impact on convulsion, while modulating D2 receptor did not affect their effects. The combination of A1 agonist and D2 agonist was highly effective in resisting convulsion (> 60 min vs 32.53±5.31 min, P=0.000). Exposure to HBO accelerated the metabolism of dopamine to its end products, which may be related to the enhanced activity of monoamine oxidase (MAO). Adenosine can inhibit MAO activity (0.0766±0.0150 U/mg.prot vs 0.1055±0.0086 U/mg.prot, P=0.004), maintaining a higher level of dopamine (1.820±0.379 mg/g vs 0.602±0.087 mg/g, P=0.000). The study demonstrated that dopamine plays a significant role in oxygen convulsion, and adenosine can affect dopamine metabolism. The interaction between them can have a crucial impact on the occurrence of oxygen convulsion. The findings offer a novel perspective for further investigating the mechanism of oxygen convulsion and exploring effective preventive strategies.

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腺苷和多巴胺在调节中枢神经系统氧毒性后果中的相互作用。
高压氧(HBO)是指绝对压力大于 1 个大气压(ATA)的纯氧,当压力过高时,可引起惊厥发作。有研究表明,腺苷和多巴胺与高压氧诱发的惊厥发作密切相关,其受体在神经细胞膜上呈现出相互拮抗的共存关系。我们探讨了腺苷和多巴胺相互作用对氧气惊厥发生的影响。将大鼠分别暴露于 6 ATA 的 HBO 中,并分别和联合使用腺苷、多巴胺及其受体调节剂进行治疗,记录惊厥发生的潜伏期。此外,在给大鼠注射腺苷并将其暴露于 HBO 30 分钟后,还测定了多巴胺及其代谢物的含量,以及与其代谢有关的酶的活性。结果显示,多巴胺能有效抑制惊厥(> 60 分钟 vs 32.53±5.31 分钟,P=0.000),而小剂量腺苷能部分抵消多巴胺的作用(> 60 分钟 vs 28.18±6.24 分钟,P=0.002)。腺苷 A1 和多巴胺 D1 受体调节剂的联合使用对惊厥的发生率有显著影响。激活或抑制 A2A 受体对惊厥的影响尤为明显,而调节 D2 受体并不影响其效果。A1 受体激动剂和 D2 受体激动剂的组合对抑制惊厥非常有效(> 60 分钟 vs 32.53±5.31 分钟,P=0.000)。暴露于 HBO 会加速多巴胺向其最终产物的代谢,这可能与单胺氧化酶(MAO)的活性增强有关。腺苷可抑制 MAO 活性(0.0766±0.0150 U/mg.prot vs 0.1055±0.0086 U/mg.prot, P=0.004),维持较高的多巴胺水平(1.820±0.379 mg/g vs 0.602±0.087 mg/g,P=0.000)。研究表明,多巴胺在氧惊厥中起着重要作用,而腺苷能影响多巴胺的代谢。它们之间的相互作用会对氧惊厥的发生产生至关重要的影响。研究结果为进一步研究氧惊厥的发病机制和探索有效的预防策略提供了新的视角。
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来源期刊
CiteScore
6.00
自引率
9.10%
发文量
296
审稿时长
2-4 weeks
期刊介绍: The Journal of Applied Physiology publishes the highest quality original research and reviews that examine novel adaptive and integrative physiological mechanisms in humans and animals that advance the field. The journal encourages the submission of manuscripts that examine the acute and adaptive responses of various organs, tissues, cells and/or molecular pathways to environmental, physiological and/or pathophysiological stressors. As an applied physiology journal, topics of interest are not limited to a particular organ system. The journal, therefore, considers a wide array of integrative and translational research topics examining the mechanisms involved in disease processes and mitigation strategies, as well as the promotion of health and well-being throughout the lifespan. Priority is given to manuscripts that provide mechanistic insight deemed to exert an impact on the field.
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