论文部分内容阅读
通过活体微透析的方法研究了环噻嗪对大鼠海马谷氨酸受体／ＮＯ／ｃＧＭＰ通路的影响．局部灌流α－氨基羟甲基异唑丙酸（ＡＭＰＡ）受体脱敏阻断剂环噻嗪能引起细胞外ｃＧＭＰ水平的提高．环噻嗪的这种作用能够被ＮＯ合酶抑制剂Ｎ－硝基－Ｌ－精氨酸（Ｌ－ＮＮＡ）或选择性的可溶性鸟苷酸环化酶抑制剂１Ｈ－［１，２，４］二唑［４，３－ａ］喹喔啉－１－酮（ＯＤＱ）所阻断．在环噻嗪灌流过程中，大鼠呈现明显的痉挛前的行为变化湿狗样反应（ＷＤＳ）．由环噻嗪引起的ｃＧＭＰ增加和ＷＤＳ反应能够被Ｎ－甲基－Ｄ－天冬氨酸（ＮＭＤＡ）受体通道阻断剂甲基二苯并环庚烯亚胺（ＭＫ－８０１）或镁离子所阻断．ＡＭＰＡ受体拮抗剂６，７－二硝基喹喔啉－２，３－二酮（ＤＮＱＸ）和２，３－二羟基－６－硝基－７－氨磺酰基－苯并（ｆ）－喹喔啉（ＮＢＱＸ）可拮抗ＷＤＳ反应，但不能阻断环噻嗪引起的ｃＧＭＰ反应．这种结果表明：（１）在海马内与ＮＯ－ｃＧＭＰ通路有关的ＡＭＰＡ受体由于内源性谷氨酸的存在保持部分脱敏状态．（２）环噻嗪对ＡＭＰＡ受体脱敏的阻断作用可导致内源性ＮＭＤＡ受体的激活．
The effects of cyclothiazide on glutamate receptor / NO / cGMP pathway in hippocampus of rats were studied by in vivo microdialysis. Local perfusion of α-amino hydroxymethyl isoxazolium propionate (AMPA) receptor desensitization inhibitor cyclothiazide can cause increased levels of extracellular cGMP. This effect of cyclothiazide can be blocked by the NO synthase inhibitor N-nitro-L-arginine (L-NNA) or the selective soluble guanylate cyclase inhibitor 1H- [1,2,4 ] Oxadiazol [4,3-a] quinoxalin-1-one (ODQ). During cyclic thiazide perfusion, rats exhibited marked changes in behavior before spasm of a wet dog-like reaction (WDS). Cyclic thiazide induced cGMP increase and WDS reaction can be blocked by N-methyl-D-aspartate (NMDA) receptor channel blocker methyl dibenzocycloheptenimide (MK-801) or magnesium Ions are blocked. The AMPA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 2,3-dihydroxy-6-nitro-7- sulfamoyl-benzo (f) Quinoxaline (NBQX) antagonized the WDS reaction but did not block the cGMP reaction induced by cyclothiazide. This result suggests that: (1) AMPA receptors associated with the NO-cGMP pathway remain partially desensitized due to the presence of endogenous glutamic acid in the hippocampus. (2) The blocking effect of cyclothiazide on AMPA receptor desensitization can lead to the activation of endogenous NMDA receptor.