Ueda M, Fujii T, Kuraishi Y, Satoh M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Eur J Pharmacol. 1992 Aug 25;219(2):271-7. doi: 10.1016/0014-2999(92)90305-n.
We have shown that bifemelane augments long-term potentiation in the mossy fiber-CA3 system, but not in the Schaffer collateral-CA1 system. To elucidate the mechanism of action of bifemelane in relation to pathway-specific augmentation of long-term potentiation, we prepared a mossy fiber terminal-rich synaptosomal fraction (P3) from guinea-pig hippocampus and investigated the effect of bifemelane on the release of glutamate from these synaptosomes, using an in vitro superfusion technique. Bifemelane (0.01-1 microM) dose dependently increased the 30 mM K(+)-evoked release of glutamate from the P3 fraction, without affecting glutamate release from a conventional synaptosomal P2 fraction. This stimulatory effect of 1 microM bifemelane was abolished by 100 microM H-7, which also suppressed the increase in K(+)-evoked glutamate release by phorbol 12,13-dibutyrate (1 microM). Bifemelane (1 microM) induced the translocation of protein kinase C activity from cytosol to membrane in the P3 fraction (which contains large and irregular-shaped synaptosomes probably derived from mossy fiber terminals), but not in the P2 fraction. These findings suggest that bifemelane directly acts on mossy fiber terminals to potentiate depolarization-induced glutamate release, which may be at least partly mediated by the translocation (activation) of protein kinase C.
我们已经表明，双苯美仑可增强苔藓纤维-CA3系统中的长时程增强效应，但对海马-CA1系统中的Schaffer侧支却无此作用。为了阐明双苯美仑与长时程增强效应的通路特异性增强相关的作用机制，我们从豚鼠海马制备了富含苔藓纤维终末的突触体组分（P3），并使用体外灌流技术研究了双苯美仑对这些突触体释放谷氨酸的影响。双苯美仑（0.01 - 1微摩尔）剂量依赖性地增加了30毫摩尔钾离子诱发的P3组分中谷氨酸的释放，而不影响传统突触体P2组分中谷氨酸的释放。100微摩尔的H - 7消除了1微摩尔双苯美仑的这种刺激作用，H - 7也抑制了佛波醇12,13 - 二丁酸酯（1微摩尔）引起的钾离子诱发的谷氨酸释放增加。双苯美仑（1微摩尔）诱导P3组分（其中含有可能源自苔藓纤维终末的大的和不规则形状的突触体）中的蛋白激酶C活性从胞质溶胶转位至细胞膜，但在P2组分中未观察到这种现象。这些发现表明，双苯美仑直接作用于苔藓纤维终末，以增强去极化诱导的谷氨酸释放，这可能至少部分是由蛋白激酶C的转位（激活）介导的。
