神经肌肉接头前阻断剂川楝素抑制大鼠大脑皮层突触体谷氨酸释放(英文)

目的　阐释川楝素的作用机制 ,为了解递质解释的基本过程提供线索。方法　以大鼠大脑皮层匀浆经密度梯度离心分离获得的突触体作为研究标本 ,分别施加 5 0mmol·L- 1KCl,1.5 μmol·L- 1卡西霉素或 7.5mmol·L- 14 氨基吡啶触发谷氨酸 (Glu)释放。通过检测由Glu氧化脱氢反应与NAD+ 生成的NADH荧光变化测定Glu释放量。结果　川楝素浓度、时间依赖地显著抑制由KCl诱发的Glu释放 ,并主要抑制钙依赖性释放 ;由卡西霉素直接提升胞内钙离子浓度而诱发的Glu释放也被川楝素明显抑制。结论川楝素抑制中枢突触Glu释放 ,该效应与其导致的递质释放机制中钙离子敏感性降低有关。

Inhibition of glutamate release from rat cerebral synaptosomes by a prejunctional blocker toosendanin

AIM To elucidate the mechanism of the action of toosendanin(TSN), which may provide a new clue for understanding the basic processes involved in transmitter release. METHODS Nerve terminals (synaptosomes) from rat cerebral cortex were used as a test system to study the effects of TSN. They were isolated by discontinuous density gradient centrifugation. The secretogogues used to evoke Glu release included 50 mmol·L-1 KCl, 1.5 μmol·L-1 calcimycin and 7.5 mmol·L-1 4-aminopyridine (4-AP). Glu released from synaptosomes was determined by measuring the fluorescence of NADH produced in oxidative dehydrogenation of Glu. RESULTSTSN obviously inhibited the Glu release evoked by KCl depolarization in a concentration- and time-dependent manner. The effect mainly resulted from TSN-induced block of the Ca2+-dependent transmitter release. After TSN application the Glu release evoked by elevating intracellular free-Ca2+ concentration (Ca2+]i) with calcimycin also significantly decreased. CONCLUSIONTSN inhibited the Glu release from central synapses and the effect was assumed to be related to TSN-induced depression in the Ca2+-sensitivity of release machinery.