Kamisaki Y, Maeda K, Ishimura M, Omura H, Moriwaki Y, Itoh T
Department of Clinical Pharmacology, Faculty of Medicine, Tottori University, Yonago, Japan.
Brain Res. 1994 Apr 25;644(1):128-34. doi: 10.1016/0006-8993(94)90355-7.
Effects of nitric oxide on glutamate (Glu) release in long-term potentiation (LTP) were investigated by superfusion of conventional (P2) and large (P3) synaptosomes prepared from the rat hippocampus. Basal releasing rates of endogenous Glu from P2 and P3 fractions were 103.6 and 85.2 pmol/min/mg protein, respectively. Exposure to a depolarizing concentration of KCl (30 mM) evoked 3.58- and 4.52-fold increases in releasing rates of Glu from P2 and P3 fractions, respectively. Although the perfusion with sodium nitroprusside (NP, 10(-3) M), a nitric oxide-releasing agent, failed to augment the K(+)-evoked releases of Glu from P2 and P3 synaptosomes, NP enhanced that from slices of the hippocampus by 39% without changing basal release. Similarly, 8-bromoguanosine 3':5'-cyclic monophosphate (10(-4) M) increased the K(+)-evoked release of Glu from slices by 30%, but not from either synaptosomes. When synaptosomes were prepared from the hippocampus which was pretreated with two trains of electrical field stimulation (100 Hz, 0.1 ms, for 2 s), K(+)-evoked releases of Glu from P2 and P3 synaptosomes were increased by 15% and 23%, respectively. Although nitric oxide is postulated to function as a retrograde messenger to maintain LTP, present results suggest that nitric oxide may not directly act upon nerve terminals to enhance glutamate release, but that interventions of glias and short neurons may be involved in the presynaptic mechanism of LTP.
通过对从大鼠海马体制备的常规（P2）和大型（P3）突触体进行灌流，研究了一氧化氮对长时程增强（LTP）中谷氨酸（Glu）释放的影响。P2和P3组分中内源性Glu的基础释放速率分别为103.6和85.2 pmol/分钟/毫克蛋白质。暴露于去极化浓度的氯化钾（30 mM）分别使P2和P3组分中Glu的释放速率增加了3.58倍和4.52倍。尽管用一氧化氮释放剂硝普钠（NP，10⁻³ M）灌流未能增强P2和P3突触体中钾离子诱发的Glu释放，但NP在不改变基础释放的情况下使海马切片中的Glu释放增强了39%。同样，8-溴鸟苷3':5'-环磷酸（10⁻⁴ M）使切片中钾离子诱发的Glu释放增加了30%，但对任何一种突触体均无此作用。当从经过两串电场刺激（100 Hz，0.1 ms，持续2 s）预处理的海马体制备突触体时，P2和P3突触体中钾离子诱发的Glu释放分别增加了15%和23%。尽管一氧化氮被假定作为逆行信使来维持LTP，但目前的结果表明，一氧化氮可能不会直接作用于神经末梢以增强谷氨酸释放，而是胶质细胞和短神经元的干预可能参与了LTP的突触前机制。
