鸟苷酸环化酶抑制剂对大鼠海马NO—cGMP信号转导的作用

The effect of selectiue inhibitor of soluble guanylyl cyclase on nitric oxide-cyclic GMP signaling

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lH—〔1,2 ,4〕口恶二唑〔4,3—a〕喹喔啉— 1—酮 (ODQ)为工具药研究大鼠海马NO—cGMP信号转导。海马内局部灌流ODQ 10 ,5 0 ,10 0 μmol/L ,5 μl/min可剂量依赖性降低细胞外基础cGMP水平 ,ODQ10 0 μmol/L作用最强 ,最大可使细胞外基础cGMP水平降低 5 0 %。ODQ10 0 μmol/L可完全对抗N—甲基—D天冬氨酸 (NMDA ,2 5 0 μmol/L)引起的细胞cGMP水平增加。本研究实验结果表明 (1)在基础状态下海马的cGMP5 0 %来源于NO依赖的可溶性鸟苷酸环化酶的激活。(2 )进一步证明了在大鼠海马NO也是通过激活可溶性鸟苷酸环化酶使cGMP增加的。

The nitric oxide-cyclic GMP signalling transduction was studied with a selective inhibitor of soluble guanylyl cyclase,1H(1,2,4)oxadiazolo 〔4,3-a〕 quinoxalin-l-one(ODQ),during microdialysis of the rat hippocampus.Intrahippocamal infusion of ODQ 10,50,100μmol/L inhibited,in a concentration-dependent manner,the basic extracellular level of cGMP.The maximal inhibition amounted to 50%.ODQ 100μmol/L completely inhibited the cGMP elevation evoked by N-methyl-D-aspartate (NMDA,250 μmol/L).The results suggest that(1)Under basic condition,about 50% of the cGMP in the hippocampus seem to originate from the soluble guanylyl cyclase.(2)It was proved further that NO elicits cGMP accumulation in target cells by stimulating soluble guanylyl cyclase in the hippocampus.