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

基本信息

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

项目摘要

(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）我们已经检查了在慢性电阻式呼吸期间，在大鼠大鼠脑皮质中，前脑脑（PPE）-A的mRNA变化。 Northern印迹显示，气道狭窄3天后诱导了PPE-A mRNA，诱导持续至少2周。原位杂交表明，PPE-A逐渐在额叶皮层中诱导。这些结果表明，内源性阿片类药物系统可能是一种重要的补偿性机制，可以减少慢性呼吸胁迫期间的呼吸感。（2）我们已经研究了在低碳酸或缺氧期间大鼠大脑大脑的乙酰胆碱（ACH）释放。 10％的CO_2在次生和下丘脑中诱导ACH，但在纹状体中没有诱导。缺氧在同一区域增加了ACH，但程度远小于高碳酸血症。（3）我们在缺氧期间通过使用体内微透析测量了在缺氧期间大鼠脑的谷氨酸（GLU）释放。在缺氧期间或在颈动脉体内完整大鼠中谷氨酸升高，但在双侧颈动脉身体切除术中没有增加。将谷氨酸显微注射到NTS中增加了通风。 NMDA受体拮抗剂MK801在NTS中灌注，在低氧造成期间阻止了通气增加。这些结果表明，谷氨酸可能是NTS中的神经递质，因为在缺氧过程中响应周围化学感受器的激活。