EVIDENCE THAT AMPHETAMINE AND NA+ GRADIENT REVERSAL INCREASE STRIATAL SYNAPTOSOMAL DOPAMINE SYNTHESIS THROUGH CARRIER-MEDIATED EFFLUX OF DOPAMINE
EVIDENCE THAT AMPHETAMINE AND NA+ GRADIENT REVERSAL INCREASE STRIATAL SYNAPTOSOMAL DOPAMINE SYNTHESIS THROUGH CARRIER-MEDIATED EFFLUX OF DOPAMINE
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DOI：
10.1016/0006-2952(86)90396-5
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发表时间：
1986-09-15
影响因子：
5.8
通讯作者：
KUCZENSKI, R
中科院分区：
文献类型：
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作者：
CONNOR, CE;KUCZENSKI, R
安非他明 (AMPH) 从纹状体突触体释放多巴胺 (DA)，并同时增加 DA 合成。由于 AMPH 可能通过逆转 DA 摄取系统而通过载体介导的扩散释放 DA，因此 DA 合成的增加可能取决于功能性摄取载体。与这种机制一致，摄取抑制剂诺米芬辛 (NMF) 和苯甲托品 (BZT) 在已知抑制 DA 摄取的浓度下完全阻止了 AMPH 诱导的 DA 合成增加。突触体膜上 Na+ 梯度的变化也会促进 DA 释放，因为 DA 和 Na+ 由神经元摄取载体共同转运。在 Na+ 含量逐渐减少的培养基中孵育突触体会增加 DA 合成，在 128 至 20 mM 范围内与 Na+ 成反比。类似地，在 10-4 M 哇巴因存在下孵育以抑制 Na+、K+-ATP 酶并允许 Na+ 在细胞内积累，也增加了 DA 合成。 BZT 也可以阻止 DA 合成的这些变化，并且与 AMPH 诱导的 DA 合成增加无关。然而，乌巴因浓度（10-6 M）本身不会增加 DA 合成，也不会促进 DA 释放，但会增强 AMPH 诱导的 DA 合成增加。此外，所有三种操作促进的 DA 合成增加仅略微依赖于培养介质中 Ca2+ 的存在。然而，在 5 和 10 mM Na+ 下，观察到增加 DA 合成的第二种成分，该成分对 BZT 不敏感，但可通过去除 Ca2+ 来阻止。这些结果表明，DA 合成的增加，以及可能由 AMPH、Na+ 降低和哇巴因促进的 DA 释放，取决于神经元膜内表面 DA 载体的可用性以及 Na+ 的细胞内含量。增加 DA 合成的第二个成分在 5 和 10 mM Na+ 时很明显，我们根据 DA 合成中可能的 Ca2+ 介导的变化进行讨论，该变化与 DA 载体无关。
Amphetamine (AMPH) releases dopamine (DA) from striatal synaptosomes and concomitantly increases DA synthesis. Since AMPH may release DA through carrrier-mediated diffusion via reversal of the DA uptake system, the increase in DA synthesis might depend on a functioning uptake carrier. Consistent with such a mechanism, the uptake inhibitors nomifensine (NMF) and benztropine (BZT) completely prevented the AMPH-induced increase in DA synthesis at concentrations known to inhibit DA uptake. Changes in the Na+ gradient across the synaptosomal membrane also promote DA release, since DA and Na+ are cotransported by the neuronal uptake carrier. Incubation of synaptosomes in medium containing decreasing Na+ increased DA synthesis inversely proportional to Na+ over the range 128 to 20 mM. Similarly, incubations in the presence of 10-4 M ouabain to inhibit Na+, K+-ATPase and allow intracellular accumulation of Na+ also increased DA synthesis. These changes in DA synthesis could also be prevented by BZT and were non-additive with the AMPH-induced increase in DA synthesis. However, a concentration of ouabain (10-6 M) which by itself did not increase DA synthesis, and does not promote DA release, potentiated the AMPH-induced increase in DA synthesis. Further, the increased DA synthesis promoted by all three manipulations was only marginally dependent on the presence of Ca2+ in the incubation medium. However, at 5 and 10 mM Na+, a second component of increased DA synthesis was observed which was insensitive to BZT, but was prevented by Ca2+ removal. These results suggest that the increase in DA synthesis, and presumably DA release promoted by AMPH, lowered Na+, and ouabain, depend on the availability of the DA carrier at the internal face of the neuronal membrane and the intracellular content of Na+. The second component of increased DA synthesis which is evident at 5 and 10 mM Na+ is discussed in terms of a possible Ca2+-mediated change in DA synthesis which is independent of the DA carrier.