Connor C E, Kuczenski R
Biochem Pharmacol. 1986 Sep 15;35(18):3123-30. doi: 10.1016/0006-2952(86)90396-5.
Amphetamine (AMPH) releases dopamine (DA) from striatal synaptosomes and concomitantly increases DA synthesis. Since AMPH may release DA through carrier-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.
苯丙胺（AMPH）可从纹状体突触体中释放多巴胺（DA），并同时增加DA的合成。由于AMPH可能通过使DA摄取系统逆转，以载体介导的扩散方式释放DA，因此DA合成的增加可能依赖于正常运作的摄取载体。与这种机制一致的是，摄取抑制剂诺米芬辛（NMF）和苯海索（BZT）在已知可抑制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。在含Na +浓度递减的培养基中孵育突触体，在128至20 mM范围内，DA合成的增加与Na +呈反比。同样，在存在10（-4）M哇巴因的情况下孵育以抑制Na +，K + -ATP酶并使Na +在细胞内蓄积，也会增加DA合成。DA合成的这些变化也可被BZT阻止，并且与AMPH诱导的DA合成增加无相加作用。然而，一种浓度的哇巴因（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孵育培养基中Ca2 +的存在。然而，在5和10 mM Na +时，观察到DA合成增加的第二个成分，其对BZT不敏感，但可被去除Ca2 +阻止。这些结果表明，AMPH、降低的Na +和哇巴因促进的DA合成增加以及可能的DA释放，取决于神经元膜内表面DA载体的可用性和细胞内Na +含量。在5和10 mM Na +时明显的DA合成增加的第二个成分，根据与DA载体无关的可能的Ca2 +介导的DA合成变化进行了讨论。
