用选择性可溶性鸟苷酸环化酶抑制剂研究大鼠小脑内NO-cGMP神经通路  

Nitric oxide-cyclic GMP signalling pathway studied with a selective inhibitor of soluble guanylyl cyclase in rat cerebellum

作　　者：金英[1] 刘婉珠[1] 赵艳杰[1] 

机构地区：[1]锦州医学院药理学教研室,辽宁锦州121001

出　　处：《中国药理学与毒理学杂志》2000年第4期278-282,共5页Chinese Journal of Pharmacology and Toxicology

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.

关 键 词：NO-CGMP 神经通路 可溶性鸟苷酸 环化酶抑制剂 

分 类 号：R96[医药卫生—药理学]