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

(1)观察了慢性阻性负荷呼吸时大鼠大脑皮层脑啡肽前体前脑啡肽(PPE)-A基因表达的变化。Northern印迹结果显示，PPE-A基因在气道狭窄后3天开始表达，并持续至少2周。原位杂交显示，PPE-A在额叶皮质逐渐被诱导。这些结果表明，内源性阿片系统可能作为一种重要的代偿机制来减少慢性呼吸应激时的呼吸感觉。(2)我们研究了高碳酸血症或低氧时大鼠下丘脑、扣带回或下丘脑中乙酰胆碱(Ach)的释放。10%CO_2可在下丘脑和下丘脑诱发30-100%的Ach，但对纹状体无明显诱导作用。在体微透析法测定缺氧时大鼠孤束核内谷氨酸(Glu)的释放。低氧或多沙普兰输注时，颈动脉体部完整的大鼠谷氨酸水平升高，而双侧颈动脉体部切除的大鼠谷氨酸水平无明显变化。NTS内微量注射谷氨酸可增加通气量。NMDA受体拮抗剂MK801在NTS内灌流可阻断缺氧性排泄时通气量的增加。这些结果提示，谷氨酸可能是孤束核在低氧时激活外周化学感受器的一种神经递质。

(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.