Taglialatela M, Amoroso S, Canzoniero L M, Di Renzo G F, Annunziato L
Institute of Pharmacology, 2nd School of Medicine, University of Naples, Italy.
J Pharmacol Exp Ther. 1988 Aug;246(2):689-94.
In the present study we investigated the effect of amiloride, a rather specific inhibitor of the membrane Na+-Ca++ exchange system, on the release of endogenous dopamine (DA) and "previously taken-up" [3H]DA from tuberoinfundibular dopaminergic neurons. Amiloride (300 microM) stimulated either endogenous DA or [3H]DA release. Amiloride-induced stimulation of [3H]DA release was prevented in a Ca++-free plus ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid medium. Amiloride, at the same concentration, reinforced both high K+- and electrically-induced stimulation of [3H]DA release. These results are explained on the basis of the ability of amiloride in blocking the Na+-Ca++ exchange system, therefore causing an elevation of intracellular Ca++ levels in resting conditions, and a further accumulation of Ca++ ions after high K+- or electrically elicited opening of voltage-operated channels specific for Ca++ ions. The enhanced intracellular Ca++ availability may trigger the stimulation of neurotransmitter release. In addition, amiloride was able to block in a dose-dependent manner (70-300 microM) the ouabain-induced [3H]DA release, suggesting that, when intracellular concentrations of Na+ are increased by the blockade of Na+,K+-adenosine triphosphatase the Na+-Ca+;+ exchange carrier reverses its resting mode of operation, mediating the influx of extracellular Ca++ ions. Amiloride, by blocking the Na+-Ca++ exchange mechanism, prevents the ouabain-elicited entrance of extracellular Ca++ ions, therefore inhibiting [3H]DA release stimulated by the cardioactive glycoside. Collectively, the results of the present study seem to be compatible with the idea that the Na+-Ca++ exchange mechanism is involved in the regulation of [3H]DA release from tuberoinfundibular dopaminergic neurons, through the regulation of Ca++ movements across the plasma membrane.
在本研究中，我们研究了氨氯吡咪（一种相当特异的膜钠钙交换系统抑制剂）对来自结节漏斗多巴胺能神经元的内源性多巴胺（DA）释放以及“先前摄取的”[3H]DA释放的影响。氨氯吡咪（300微摩尔）刺激了内源性DA或[3H]DA的释放。在无钙加乙二醇双（β-氨基乙基醚）-N，N'-四乙酸培养基中，氨氯吡咪诱导的[3H]DA释放刺激被阻止。相同浓度的氨氯吡咪增强了高钾和电刺激引起的[3H]DA释放。这些结果基于氨氯吡咪阻断钠钙交换系统的能力得到解释，因此在静息状态下导致细胞内钙离子水平升高，并且在高钾或电刺激引起钙离子特异性电压门控通道开放后导致钙离子进一步积累。细胞内钙离子可用性的增强可能触发神经递质释放的刺激。此外，氨氯吡咪能够以剂量依赖性方式（70 - 300微摩尔）阻断哇巴因诱导的[3H]DA释放，这表明当通过阻断钠钾-腺苷三磷酸酶使细胞内钠离子浓度增加时，钠钙交换载体逆转其静息操作模式，介导细胞外钙离子的内流。氨氯吡咪通过阻断钠钙交换机制，阻止了哇巴因引起的细胞外钙离子内流，从而抑制了强心苷刺激的[3H]DA释放。总体而言，本研究结果似乎与以下观点一致，即钠钙交换机制通过调节钙离子跨质膜的移动参与结节漏斗多巴胺能神经元[3H]DA释放的调节。
