一氧化氮抑制海马神经元兴奋的机制研究

THE INHIBITIVE EFFECT OF NITRIC OXIDE ON HIPPOCAMPAL NEURONS EXCITATION

研究青霉素诱发培养的海马CA1区神经元细胞产生的一氧化氮 (NO)在兴奋过程中的抑制机制。用激光扫描共聚焦显微镜观察发现1000IU/ml的青霉素可诱发一种晚而慢的NO合成模式。NO合成酶抑制剂L -NNA(0 -10μmol/L)可剂量依赖地抑制NO的合成 ,并促进谷氨酸水平的升高。同时发现L -NNA(1、10μmol/L)可显著促进蛋氨酸脑啡肽 (M -ENK)的升高 ,而对强啡肽 -B(DYN -B)的水平没有影响。100μmol/L的β-FNA(一种M -ENK受体抑制剂 )可抑制L -NNA诱导的谷氨酸水平的升高 ,而100μmol/L的nor -BIN (一种DYN受体抑制剂 )对此没有影响。以上结果提示 :1000IU/ml的青霉素诱导合成的NO可通过抑制M -ENK水平来抑制神经元的兴奋。

The inhibitive effect of nitric oxide(NO) on cultured rat hippocampal CA1 neurons excitation stimulated by penicillin G(PG) was investigated. A slow and late type of intracellular NO production induced by PG(1000 IU/ml) was disclosed when monitored with laser scanning confocal microscopy (LSCM). Pretreatment of L-NNA(0-10μmol/L), an NO synthase inhibitor, could dose-dependently inhibit the NO production and increase the intercellular level glutamate(10min after PG stimulation) as well. L-NNA(0-10μmol/L) also tended to increase the immunoreactive methionine enkephalin(ir-M-ENK) level while the immunoreactive dynorphin B(ir-DYN-B) level was remained unchanged. Finally, β-FNA (100μmol/L, an M-ENK receptor inhibitor) but not nor-BIN(100μmol/L, a DYN receptor inhibitor) could inhibit the increase of intercellular level glutamate caused by L-NNA. Together, the following conclusion was made: NO induced by PG (1000 IU/ml) stimulation inhibit further neuron excitation by inhibit the level of M-ENK.