Rodríguez de Lores Arnaiz G
Instituto de Biología Celular, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Mol Neurobiol. 1992 Winter;6(4):359-75. doi: 10.1007/BF02757941.
The arrival of the nerve impulse to the nerve endings leads to a series of events involving the entry of sodium and the exit of potassium. Restoration of ionic equilibria of sodium and potassium through the membrane is carried out by the sodium/potassium pump, that is the enzyme Na+,K(+)-ATPase. This is a particle-bound enzyme that concentrates in the nerve ending or synaptosomal membranes. The activity of Na+,K(+)-ATPase is essential for the maintenance of numerous reactions, as demonstrated in the isolated synaptosomes. This lends interest to the knowledge of the possible regulatory mechanisms of Na+,K(+)-ATPase activity in the synaptic region. The aim of this review is to summarize the results obtained in the author's laboratory, that refer to the effect of neurotransmitters and endogenous substances on Na+,K(+)-ATPase activity. Mention is also made of results in the field obtained in other laboratories. Evidence showing that brain Na+,K(+)-ATPase activity may be modified by certain neurotransmitters and insulin have been presented. The type of change produced by noradrenaline, dopamine, and serotonin on synaptosomal membrane Na+,K(+)-ATPase was found to depend on the presence or absence of a soluble brain fraction. The soluble brain fraction itself was able to stimulate or inhibit the enzyme, an effect that was dependent in turn on the time elapsed between preparation and use of the fraction. The filtration of soluble brain fraction through Sephadex G-50 allowed the separation of two active subfractions: peaks I and II. Peak I increased Na+,K(+)- and Mg(2+)-ATPases, and peak II inhibited Na+,K(+)-ATPase. Other membrane enzymes such as acetylcholinesterase and 5'-nucleotidase were unchanged by peaks I or II. In normotensive anesthetized rats, water and sodium excretion were not modified by peak I but were increased by peak II, thus resembling ouabain effects. 3H-ouabain binding was unchanged by peak I but decreased by peak II in some areas of the CNS assayed by quantitative autoradiography and in synaptosomal membranes assayed by a filtration technique. The effects of peak I and II on Na+,K(+)-ATPase were reversed by catecholamines. The extent of Na+,K(+)-ATPase inhibition by peak II was dependent on K+ concentration, thus suggesting an interference with the K+ site of the enzyme. Peak II was able to induce the release of neurotransmitter stored in the synaptic vesicles in a way similar to ouabain. Taking into account that peak II inhibits only Na+,N(+)-ATPase, increases diuresis and natriuresis, blocks high affinity 3H-ouabain binding, and induces neurotransmitter release, it is suggested that it contains an ouabain-like substance.
神经冲动到达神经末梢会引发一系列事件，包括钠的内流和钾的外流。通过细胞膜恢复钠和钾的离子平衡是由钠/钾泵完成的，即Na⁺,K⁺-ATP酶。这是一种与颗粒结合的酶，集中在神经末梢或突触体膜中。如在分离的突触体中所证实的，Na⁺,K⁺-ATP酶的活性对于维持众多反应至关重要。这使得了解突触区域中Na⁺,K⁺-ATP酶活性可能的调节机制变得很有意义。本综述的目的是总结作者实验室获得的结果，这些结果涉及神经递质和内源性物质对Na⁺,K⁺-ATP酶活性的影响。还提及了其他实验室在该领域获得的结果。已经提出证据表明脑Na⁺,K⁺-ATP酶活性可能会被某些神经递质和胰岛素所改变。发现去甲肾上腺素、多巴胺和5-羟色胺对突触体膜Na⁺,K⁺-ATP酶产生的变化类型取决于可溶性脑组分的存在与否。可溶性脑组分本身能够刺激或抑制该酶，这种作用又取决于该组分制备和使用之间经过的时间。通过葡聚糖凝胶G-50对可溶性脑组分进行过滤，可以分离出两个活性亚组分：峰I和峰II。峰I增加了Na⁺,K⁺-和Mg²⁺-ATP酶的活性，而峰II抑制了Na⁺,K⁺-ATP酶的活性。其他膜酶如乙酰胆碱酯酶和5'-核苷酸酶不受峰I或峰II的影响。在血压正常的麻醉大鼠中，峰I不改变水和钠的排泄，但峰II会增加水和钠的排泄，因此类似于哇巴因的作用。通过定量放射自显影测定的中枢神经系统某些区域以及通过过滤技术测定的突触体膜中，³H-哇巴因结合不受峰I影响，但被峰II降低。峰I和峰II对Na⁺,K⁺-ATP酶的作用被儿茶酚胺逆转。峰II对Na⁺,K⁺-ATP酶的抑制程度取决于K⁺浓度，因此表明对该酶的K⁺位点有干扰。峰II能够以类似于哇巴因的方式诱导储存在突触小泡中的神经递质释放。考虑到峰II仅抑制Na⁺,K⁺-ATP酶，增加利尿和利钠作用，阻断高亲和力³H-哇巴因结合，并诱导神经递质释放，提示它含有一种类似哇巴因的物质。
