Bentué-Ferrer D, Decombe R, Saïag B, Allain H, Van den Driessche J
Laboratoire de Pharmacologie, UFR Médicale, Rennes, France.
Exp Brain Res. 1993;93(2):288-92. doi: 10.1007/BF00228396.
Cerebral ischaemia induces considerable neurotransmitter exocytosis, mediated by calcium entry in neurones, essentially via the N-type, voltage-dependent channels, which are insensitive to calcium blockers. Nonetheless, these blockers, by unclear mechanisms, exert a neuroprotective effect when used in experimental ischaemic models. On the other hand, the existence of L-type, voltage-dependent channels, the only ones responding to the action of calcium blockers on synapses, argues in favour of their possible concomitant action in certain highly pathological situations. We studied the action of three calcium blockers, nimodipine, diltiazem and verapamil (administered at a concentration of 100 microM directly into the striatum of rats), on the extracellular release of dopamine and serotonin, and on the level of their main metabolites, in a model of transient global cerebral ischaemia (four-vessel occlusion). The total absence of effect of these molecules on neurotransmitter release induced by ischaemia proves the non-involvement of this mechanism in the protective action of calcium entry blockers on ischaemic lesions, and the absence or very weak action of L-type, voltage-dependent presynaptic channels in the striatum of rats.
脑缺血会引发大量神经递质的胞吐作用，这一过程由神经元内的钙内流介导，主要通过对钙通道阻滞剂不敏感的N型电压依赖性通道。尽管如此，这些阻滞剂通过不明机制，在实验性缺血模型中使用时会发挥神经保护作用。另一方面，L型电压依赖性通道存在，它是唯一对钙通道阻滞剂作用于突触有反应的通道，这表明在某些高度病理情况下它们可能会协同发挥作用。我们研究了三种钙通道阻滞剂，尼莫地平、地尔硫䓬和维拉帕米（以100微摩尔的浓度直接注入大鼠纹状体），在短暂性全脑缺血（四血管闭塞）模型中对多巴胺和5-羟色胺细胞外释放及其主要代谢产物水平的影响。这些分子对缺血诱导的神经递质释放完全没有作用，这证明该机制不参与钙内流阻滞剂对缺血性损伤的保护作用，且大鼠纹状体中L型电压依赖性突触前通道不存在或作用非常微弱。
