Konoki K, Hashimoto M, Nonomura T, Sasaki M, Murata M, Tachibana K
Department of Chemistry, School of Science, University of Tokyo, Japan.
J Neurochem. 1998 Jan;70(1):409-16. doi: 10.1046/j.1471-4159.1998.70010409.x.
45Ca2+ influx in rat glioma C6 cells induced by 0.3 nM maitotoxin (MTX) was markedly inhibited by brevetoxin A (PbTx1) and brevetoxin B (PbTx2), with EC50 values of 16 and 13 microM, respectively. This inhibition was observed immediately after addition of MTX when monitored with fura-2, which suggests that PbTx2 directly blocks the action of MTX. This blockade by PbTx2 was not affected by tetrodotoxin, which excludes the involvement of voltage-sensitive sodium channels. The depolarizing effects of these brevetoxins were also not a likely cause of this inhibition, because melittin, a channel-forming peptide, did not significantly block MTX-induced 45Ca2+ influx. Instead, this inhibition was thought to be mediated by blockade of an MTX-binding site by the brevetoxins, based on the fact that these toxins, particularly PbTx2, closely mimic the partial structure of MTX. Synthetic fragments of MTX corresponding to the hydrophilic EF-GH rings (200 microM) and LM-NO rings (500 microM) of MTX significantly reduced MTX-elicited Ca2+ influx. The observation that the effects of MTX were inhibited by structural mimics of both its hydrophobic and hydrophilic portions implies that both portions of the MTX molecule recognize its target.
0.3 nM 刺尾鱼毒素（MTX）诱导的大鼠胶质瘤C6细胞中45Ca2+内流受到短裸甲藻毒素A（PbTx1）和短裸甲藻毒素B（PbTx2）的显著抑制，其半数有效浓度（EC50）值分别为16和13 μM。当用fura-2监测时，在加入MTX后立即观察到这种抑制作用，这表明PbTx2直接阻断了MTX的作用。PbTx2的这种阻断作用不受河豚毒素的影响，这排除了电压敏感性钠通道的参与。这些短裸甲藻毒素的去极化作用也不太可能是这种抑制的原因，因为成孔肽蜂毒素并未显著阻断MTX诱导的45Ca2+内流。相反，基于这些毒素，特别是PbTx2，紧密模拟MTX的部分结构这一事实，认为这种抑制是由短裸甲藻毒素对MTX结合位点的阻断介导的。与MTX的亲水性EF-GH环（200 μM）和LM-NO环（500 μM）相对应的MTX合成片段显著降低了MTX引发的Ca2+内流。MTX的作用受到其疏水和亲水部分的结构模拟物抑制这一观察结果表明，MTX分子的这两个部分都能识别其靶点。
