Taglialatela M, Amoroso S, Kaparos G, Maurano F, 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):682-8.
In the present study we investigated the membrane events and the ionic processes which mediate the stimulatory effect of ouabain on the release of endogenous dopamine (DA) and "previously taken-up" [3H]DA release from rat hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons. Ouabain (0.1-1 mM) dose-dependently stimulated endogenous DA and "newly taken-up" [3H]DA release. This effect was counteracted partially by nomifensine (10 microM). Removal of Ca++ ions from the extracellular space in the presence of the Ca++-chelator ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid prevented completely ouabain-elicited [3H]DA release. Lanthanum (1 mM) and cobalt (2 mM), two inorganic Ca++-entry blockers, were able to inhibit this stimulatory effect, whereas verapamil (10 microM) and nitrendipine (50 microM), two organic antagonists of the voltage-operated channel for Ca++ ions, failed to affect ouabain-induced [3H]DA release. By contrast, adriamycin (100-300 microM), a putative inhibitor of cardiac Na+-Ca++ antiporter, dose-dependently prevented ouabain-induced [3H]DA release from TIDA neurons. Finally, tetrodotoxin reduced digitalis-stimulated [3H]DA release. In conclusion, these results seem to be compatible with the idea that the inhibition of Na+,K+-adenosine triphosphatase by ouabain stimulates the release of [3H]DA from a central neuronal system like the TIDA tract and that this effect is critically dependent on the entrance of Ca++ ions into the nerve terminals of these neurons. In addition the Na+-Ca++ exchange antiporter appears to be the membrane system which transports Ca++ ions into the neuronal cytoplasm during Na+,K+-adenosine triphosphatase inhibition. The enhanced intracellular Ca++ availability triggers DA release which could occur partially through a carrier-dependent process.
在本研究中，我们探究了介导哇巴因对大鼠下丘脑结节漏斗多巴胺能（TIDA）神经元释放内源性多巴胺（DA）及“先前摄取的”[3H]DA的刺激作用的膜事件和离子过程。哇巴因（0.1 - 1 mM）以剂量依赖的方式刺激内源性DA及“新摄取的”[3H]DA的释放。诺米芬辛（10 μM）可部分抵消这种作用。在存在Ca++螯合剂乙二醇双（β - 氨基乙基醚）-N，N'-四乙酸的情况下，从细胞外空间去除Ca++离子可完全阻止哇巴因引发的[3H]DA释放。镧（1 mM）和钴（2 mM）这两种无机Ca++内流阻滞剂能够抑制这种刺激作用，而维拉帕米（10 μM）和尼群地平（50 μM）这两种Ca++离子电压门控通道的有机拮抗剂未能影响哇巴因诱导的[3H]DA释放。相比之下，阿霉素（100 - 300 μM），一种推测的心脏Na+-Ca++反向转运体抑制剂，以剂量依赖的方式阻止了哇巴因诱导的TIDA神经元释放[3H]DA。最后，河豚毒素降低了洋地黄刺激的[3H]DA释放。总之，这些结果似乎与以下观点相符：哇巴因对Na +，K+-腺苷三磷酸酶的抑制作用刺激了来自像TIDA束这样的中枢神经系统的[3H]DA释放，并且这种作用严重依赖于Ca++离子进入这些神经元的神经末梢。此外，Na+-Ca++交换反向转运体似乎是在Na +，K+-腺苷三磷酸酶抑制期间将Ca++离子转运到神经元细胞质中的膜系统。细胞内Ca++可用性的增加触发了DA释放，这可能部分通过载体依赖过程发生。
