The Anti-Botulism Triterpenoid Toosendanin Elicits Calcium Increase and Exocytosis in Rat Sensory Neurons
The Anti-Botulism Triterpenoid Toosendanin Elicits Calcium Increase and Exocytosis in Rat Sensory Neurons
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抗肉毒中毒三萜川楝素引起大鼠感觉神经元钙增加和胞吐作用
DOI：
10.1007/s10571-011-9716-z
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发表时间：
2011-11-01
影响因子：
4
通讯作者：
Cui, Zong Jie
中科院分区：
文献类型：
--
作者：
Fang, Xiao Feng;Cui, Zong Jie
Toosendanin是一种来自melia toosendan Sieb et Zucc的三萜，以前被发现是一种有效的抗肉毒杆菌剂，在运动神经末端和中枢突触都有双相作用：最初的促进，然后是长期的抑制。最初的促进作用可能是由于电压依赖性钙通道的激活加上钾通道的抑制，但其抑制作用尚不完全清楚。仙丹素对不可兴奋性胰腺腺泡细胞的胞内钙或分泌没有影响，排除了仙丹素对胞外分泌的一般抑制作用。本研究研究了仙丹素对大鼠结节神经节感觉神经元的影响。结果发现，仙丹素对胞质钙和神经元胞吐的增加具有剂量依赖性。膜电位指示剂双-（1,3-二丁基巴比妥酸）三甲氧醇实验发现，toosendanin对辣椒素不敏感的神经元进行超极化，但对辣椒素敏感的神经元去极化；高钾诱导的高钙增加在超极化神经元中比在去极化神经元中要小得多，而钾诱导的去极化在这两种类型的神经元中没有差异。在表现自发钙振荡的神经元中，仙丹素增加了振荡幅度，但没有增加频率。在无钙缓冲液、硝苯地平和瞬时受体电位香草样蛋白1 （TRPV1）拮抗剂辣椒平中，toosendanin诱导的钙升高降低。同时测定细胞质和内质网钙显示细胞质钙增加，内质网钙减少，表明仙丹素触发内质网钙释放。这些数据共同表明，仙丹素调节感觉神经元，但对膜电位有相反的影响，这取决于辣椒素受体/TRPV - 1通道的存在与否。
Toosendanin, a triterpenoid fromMelia toosendan Sieb et Zucc, has been found before to be an effective anti-botulism agent, with a bi-phasic effect at both motor nerve endings and central synapse: an initial facilitation followed by prolonged depression. Initial facilitation may be due to activation of voltage-dependent calcium channels plus inhibition of potassium channels, but the depression is not fully understood. Toosendanin has no effect on intracellular calcium or secretion in the non-excitable pancreatic acinar cells, ruling out general toosendanin inhibition of exocytosis. In this study, toosendanin effects on sensory neurons isolated from rat nodose ganglia were investigated. It was found that toosendanin stimulated increases in cytosolic calcium and neuronal exocytosis dose dependently. Experiments with membrane potential indicator bis-(1,3-dibutylbarbituric acid)trimethine oxonol found that toosendanin hyperpolarized capsaicin-insensitive but depolarized capsaicin-sensitive neurons; high potassium-induced calcium increase was much smaller in hyperpolarizing neurons than in depolarizing neurons, whereas no difference was found for potassium-induced depolarization in these two types of neurons. In neurons showing spontaneous calcium oscillations, toosendanin increased the oscillatory amplitude but not frequency. Toosendanin-induced calcium increase was decreased in calcium-free buffer, by nifedipine, and by transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine. Simultaneous measurements of cytosolic and endoplasmic reticulum (ER) calcium showed an increase in cytosolic but a decrease in ER calcium, indicating that toosendanin triggered ER calcium release. These data together indicate that toosendanin modulates sensory neurons, but had opposite effects on membrane potential depending on the presence or absence of capsaicin receptor/TRPV 1 channel.