摘要
应用清醒大鼠脑微透析技术以选择性可溶性鸟苷酸环化酶抑制剂 1 H- [1 ,2 ,4]口恶二唑 [4,3- a]喹喔啉 - 1 -酮 ( ODQ)为工具药研究大鼠小脑 NO-c GMP神经通路 .小脑内局部灌流 ODQ( 5,1 0 ,50 ,1 0 0 μmol· L-1,5μL·min-1)可剂量依赖性降低细胞外基础 c GMP水平 ,最大可使细胞外基础 c GMP水平降低 80 % .ODQ1 0 0 μmol· L-1可完全对抗N -甲基 - D-天冬氨酸 ( NMDA,2 0 0μmol· L-1)或α-氨基羟甲基异口恶唑丙酸 ( AMPA,1 0 0μmol· L-1)引起的细胞外 c GMP水平增加 ,ODQ也可抑制 NO供体 S-亚硝基 - N-乙酰青霉胺 ( SNAP,1 .5mmol·L-1)引起的细胞外 c GMP水平增加 .说明在基础条件下小脑内 c GMP80 %来源于可溶性鸟苷酸环化酶激活 .进一步证明了 NO通过激活可溶性鸟苷酸环化酶使 c GMP增加 .
The nitric oxide(NO) cGMP signalling pathway in rat cerebellum was studied with a selective inhibitor of soluble guanylyl cyclase, 1H [1,2,4]oxadiazolo[4,3 a]quinoxalin 1 one (ODQ), and microdialysis. Intracerebellar infusion of ODQ (5, 10, 50, 100 μmol·L -1 , 5 μL·min -1 ) inhibited, in a concentration dependent manner, the basal extracellular level of cGMP. The maximal inhibition was 80%. ODQ 100 μmol·L -1 completely inhibited the cGMP elevation evoked by N methyl D aspartic acid (NMDA) or by α amino 3 hydroxy 5 methyl 4 isoxazolepropionic acid (AMPA). ODQ Also prevented cGMP elevation induced by NO generator S nitroso N acetylpenicillamine (SNAP, 1.5 mmol·L -1 ). The results suggest that under basal condition, about 80% of the cGMP in the cerebellum seem to originate from the soluble guanylyl cyclase. The results further suggest that NO elicit cGMP accumulation in target cells by stimulating soluble guanylyl cyclase.
出处
《中国药理学与毒理学杂志》
CSCD
北大核心
2000年第4期278-282,共5页
Chinese Journal of Pharmacology and Toxicology
关键词
NO-CGMP
神经通路
可溶性鸟苷酸
环化酶抑制剂
H [1
2
4]oxadiazolo[4
3 a]quinoxalin 1 one
cyclic GMP
cerebellum
receptors
amino acid
