Zelles T, Franklin L, Koncz I, Lendvai B, Zsilla G
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
Neurochem Res. 2001 Sep;26(8-9):1095-100. doi: 10.1023/a:1012365408215.
The alkaloid derivative vinpocetine (14-ethoxycarbonyl-(3alpha,16alpha-ethyl)-14,15-eburnamine; Cavinton) has a well known beneficial effect on brain function in hypoxic and ischemic conditions. While it increases CNS blood flow and improves cellular metabolism, relatively little is known about vinpocetine's underlying molecular mechanisms on the single cell level. Since apoptotic and necrotic cell damage is always preceded by an increase in [Ca2+]i, this study investigated the effect of vinpocetine on [Ca2+]i increases in acute brain slices. Sodium influx is an early event in the biochemical cascade that takes place during ischemia. The alkaloid veratridine can activate this Na+ influx, causing depolarization and increasing [Ca2+]i in the cells. Therefore, it can be used to simulate an ischemic attack in brain cells. Using a cooled CCD camera-based ratio imaging system and cell loading with fura 2/AM, the effect of vinpocetine on [Ca2+]i changes in single pyramidal neurons in the vulnerable CA1 region of rat hippocampal slices was investigated. Preperfusion and continuous administration of vinpocetine (10 microM) significantly inhibited the elevation in [Ca2+]i induced by veratridine (10 microM). When the drug was administered after veratridine, it could accelerate the recovery of cellular calcium levels. Piracetam, another nootropic used in clinical practice, could attenuate the elevation of [Ca2+]i only at a high, 1 mM, concentration. We have concluded that vinpocetine, at a pharmacologically relevant concentration, can decrease pathologically high [Ca2+]i levels in individual rat hippocampal CA1 pyramidal neurons; this effect might contribute to the neuroprotective property of the drug.
生物碱衍生物长春西汀（14 - 乙氧羰基 -（3α，16α - 乙基）- 14,15 - 埃博胺；卡温顿）在缺氧和缺血条件下对脑功能具有众所周知的有益作用。虽然它能增加中枢神经系统血流量并改善细胞代谢，但在单细胞水平上，人们对长春西汀潜在的分子机制了解相对较少。由于凋亡和坏死性细胞损伤总是先于细胞内钙离子浓度（[Ca2+]i）升高，本研究调查了长春西汀对急性脑切片中[Ca2+]i升高的影响。钠内流是缺血期间发生的生化级联反应中的早期事件。生物碱藜芦碱可激活这种钠内流，导致细胞去极化并增加细胞内[Ca2+]i。因此，它可用于模拟脑细胞中的缺血发作。使用基于冷却电荷耦合器件（CCD）相机的比率成像系统以及用fura 2/AM进行细胞负载，研究了长春西汀对大鼠海马切片易损CA1区单个锥体神经元中[Ca2+]i变化的影响。预先灌注并持续给予长春西汀（10微摩尔）可显著抑制藜芦碱（10微摩尔）诱导的[Ca2+]i升高。当在藜芦碱给药后给予该药物时，它可加速细胞钙水平的恢复。另一种临床实践中使用的促智药吡拉西坦仅在高浓度（1毫摩尔）时才能减弱[Ca2+]i的升高。我们得出结论，在药理学相关浓度下，长春西汀可降低单个大鼠海马CA1锥体神经元中病理性升高的[Ca2+]i水平；这种作用可能有助于该药物的神经保护特性。
