Changes in Opioid and Ach of the Rat Brain during Resistive Loaded Breathing

阻力负荷呼吸期间大鼠大脑阿片类药物和乙酰胆碱的变化

• 批准号: 04670456
• 负责人: KIKUCHI Yoshihiro
• 金额: $ 1.34万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670456/
• 关键词: Enkephaline; Acetylcholine; Microdialysis; In situ Hybridyzation; Control of breathing; Hypoxic ventilatory response; Hypercapnis; 呼吸困難

(1) We have examined changes of mRNA for preproenkephaline (PPE)-A, which is a precursor of enkephaline, in the rats cerebral cortex during chronic resistive loaded breathing. Northern blot revealed that PPE-A mRNA was induced after 3 days of airway stenosis, and the induction continued for at least 2 weeks. In situ hybridization revealed that PPE-A was gradually induced in frontal cortex. These results suggest that the endogenous opioid system may be at work as an important compensatory mechanism to reduce the reaspiratory sensation during chronic respiratory stress.(2) We have investigated acetylcholine (Ach) release in the hypocampus, cingulate cortex or hypothalamus of rat brain during hypercapnia or hypoxia. 10% CO_2 induced Ach in the hypocampus and hypothalamus by 30-100%, but it did not induced in the striatum. Hypoxia increased Ach in the same area, but the degree was much smaller than that of hypercapnia.(3) We measured glutamate (Glu) release in the nucleus tractus solitarius of rats brain during hypoxia by using in vivo microdialysis. Glutamate increased during hypoxia or during doxapram infusion in carotid body intact rats, but it did not increased in rats with bilateral carotid body resection. Microinjected glutamate into the NTS increased ventilation. MK801, a NMDA receptor antagonist, perfused in the NTS blocked the ventilatory increase during hypoxic ecposure. These results suggests that glutamate may be a neurotransmitter in the NTS in response to peripheral chemoreceptor activation during hypoxia.

(1)本文研究了慢性阻力性负荷呼吸时大鼠大脑皮层脑啡肽前体-脑啡肽原-A（PPE）mRNA的变化。北方印迹显示，气道狭窄3d后，PPE-A mRNA开始表达，并持续表达至少2周。原位杂交结果显示，PPE-A在额叶皮层逐渐被诱导表达。这些结果表明，内源性阿片系统可能在工作中作为一个重要的代偿机制，以减少在慢性呼吸应激的再呼气感觉。(2)本文观察了高碳酸血症和低氧时大鼠下海马、扣带回和下丘脑乙酰胆碱（Ach）的释放。10%CO_2可使下丘脑和下海马的Ach增加30- 100%，但对纹状体无明显影响。缺氧可使同一部位Ach升高，但幅度远小于高碳酸血症。(3)采用在体微透析技术，观察了缺氧时大鼠孤束核谷氨酸（Glu）释放的变化。谷氨酸增加在缺氧期间或在doxapram输注在颈动脉体完整的大鼠，但没有增加在大鼠双侧颈动脉体切除。孤束核内微量注射谷氨酸增加通气。孤束核内灌注NMDA受体拮抗剂MK 801可阻断缺氧兴奋时的兴奋性增加。这些结果表明，谷氨酸可能是一种神经递质在NTS在缺氧时响应外周化学感受器激活。

项目成果

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S.Okabe et al.: "Role of chemical drive in recruiting upper airway and inspiratory muscles in patients with sleep apnea." Am.Rev.,Respir.Dis.147. 190-195 (1993)

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