环噻嗪对大鼠海马cGMP释放的影响

Effect of cyclothiazide on efflux of cGMP in the hippocampus of freely-moving rats

目的及方法 应用清醒大鼠脑微透析技术研究α 氨基羟甲基异口恶唑丙酸 (AMPA)受体脱敏阻断剂环噻嗪对大鼠海马cGMP释放的影响。结果 海马局部灌流AMPA受体的激动剂AMPA 15 0 μmol/L可使细胞外cGMP水平有一定程度的提高 ,但未达到统计学意义。应用AMPA受体脱敏阻断剂环噻嗪 30 0 μmol/L可使细胞外cGMP水平明显提高。环噻嗪引起的cGMP反应可被一氧化氮合酶的阻断剂N -硝基 -L -精氨酸 15 0 μmol/L所阻断 ,也可被选择性可溶性鸟苷酸环化酶抑制剂 1H - [1,2 ,4]口恶二唑 [4 ,3 -α]喹喔啉 - 1-酮 (ODQ)5 0 μmol/L所阻断。 结论 这些结果表明在海马内与NO

Objective and Methods The effects of cyclothiazide on cGMP efflux were determined by in vivo microdialysis in the rat hippocampus. Results When α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid(AMPA) 150 μmol/L was locally infused into the hippocampus, the cGMP level only increased most animals to some extent, but not high enough for statistics. The local infusion of cyclothiazide 300 μmol/L into the rat hippocampus, a blocker of AMPA receptor desensitization, elicited the elevation of cGMP levels. The effect of cyclothiazide was blocked by local administration of the NO synthase inhibitor N G-nitro-L-arginine 150 μmol/L or the selective inhibitor of soluble guanylyl cyclase 1H-oxadiazoloquinoxalin-1-one(ODQ)50 μmol/L. Conclusion These results suggest that AMPA receptors related to the NO/cGMP pathway in the hippoca mpus are tonically activated and kept in a desensitized state by endogenous glutamate.