Amoroso S, Sensi S, di Renzo G, Annunziato L
Department of Human Communication Sciences, School of Medicine, University of Naples, Federico II, Italy.
J Pharmacol Exp Ther. 1993 Feb;264(2):515-20.
The aim of the present study was to investigate the possible role played by the Na(+)-Ca++ exchange system in the modulation of D-[3H]aspartate release induced by anoxia and glucopenia from hippocampal slices. When hippocampal slices were exposed to anoxic and glucopenic conditions (oligomycin + 2-deoxyglucose or 95% N2/5% CO2), an increase of basal D-[3H]aspartate release occurred. Two organic calcium entry blockers, verapamil and nimodipine, and the inorganic calcium entry blocker, gadolinium, did not prevent anoxia-induced D-[3H]aspartate release. In contrast, the calcium-chelator, EGTA, and lanthanum, an inorganic compound that blocks voltage-sensitive calcium channels and Na(+)-Ca++ exchanger activity, enhanced anoxia-induced D-[3H]aspartate release. In addition, the 2'-4'-dimethylbenzil amiloride derivative, a rather specific inhibitor of the Na(+)-Ca++ exchanger system, enhanced anoxia-induced D-[3H]aspartate release. Finally, tetrodotoxin, which selectively blocks the Na(+)-channels, attenuated anoxia-elicited D-[3H]aspartate release. In conclusion, the results of the present study confirmed that, under anoxic and glucopenic conditions, D-[3H]aspartate release was not dependent on the entrance of extracellular Ca++ ions through the voltage-sensitive calcium channels and demonstrated that the inhibition of the Na(+)-Ca++ antiporter enhanced excitatory amino acid release. This result seems to suggest that, when intracellular Na+ concentrations increase, because of the anoxic and glucopenic conditions, both the Na(+)-Ca++ exchanger and the Na(+)-syntransporter system of glutamate operate as Na+ ion efflux pathways. Therefore, when the antiporter is blocked, the syntransporter remains the only pathway for Na+ ion extrusion, leading to an enhancement of D-[3H]aspartate release.
本研究的目的是探讨Na(+)-Ca++交换系统在调节海马切片缺氧和低糖诱导的D-[3H]天冬氨酸释放中可能发挥的作用。当海马切片暴露于缺氧和低糖条件下（寡霉素+2-脱氧葡萄糖或95%N2/5%CO2）时，基础D-[3H]天冬氨酸释放增加。两种有机钙通道阻滞剂维拉帕米和尼莫地平以及无机钙通道阻滞剂钆，均不能阻止缺氧诱导的D-[3H]天冬氨酸释放。相反，钙螯合剂EGTA和镧（一种阻断电压敏感性钙通道和Na(+)-Ca++交换体活性的无机化合物）增强了缺氧诱导的D-[3H]天冬氨酸释放。此外，2'-4'-二甲基苄基氨氯地平衍生物（一种相当特异的Na(+)-Ca++交换体系统抑制剂）增强了缺氧诱导的D-[3H]天冬氨酸释放。最后，选择性阻断Na(+)通道的河豚毒素减弱了缺氧引起的D-[3H]天冬氨酸释放。总之，本研究结果证实，在缺氧和低糖条件下，D-[3H]天冬氨酸释放不依赖于细胞外Ca++离子通过电压敏感性钙通道的内流，并表明抑制Na(+)-Ca++反向转运体可增强兴奋性氨基酸释放。这一结果似乎表明，在缺氧和低糖条件下，当细胞内Na+浓度升高时，Na(+)-Ca++交换体和谷氨酸的Na(+)-同向转运体系统均作为Na+离子外流途径发挥作用。因此，当反向转运体被阻断时，同向转运体仍然是Na+离子外排的唯一途径，导致D-[3H]天冬氨酸释放增加。
