Department of Functional Biology and Health Sciences, Faculty of Biology, University of Vigo, Campus As Lagoas-Marcosende, 36310 Vigo, Pontevedra, Spain.
Arch Toxicol. 2010 Oct;84(10):777-85. doi: 10.1007/s00204-010-0533-9. Epub 2010 Mar 21.
The purpose of the present work was to assess the effects of glufosinate ammonium (GLA), an aminoacid structurally related to glutamate, on in vivo dopamine (DA) release from rat striatum, using brain microdialysis coupled to HPLC-EC. Intrastriatal administration of GLA produced significant concentration-dependent increases in DA levels. At least two mechanisms can be proposed to explain these increases: GLA could be inducing DA release from synaptic vesicles or producing an inhibition of DA transporter (DAT). Thus, we investigated the effects of GLA under Ca(++)-free condition, and after pretreatment with reserpine and TTX. It was observed that the pretreatment with Ca(++)-free Ringer, reserpine or TTX significantly reduced the DA release induced by GLA. Coinfusion of GLA and nomifensine shows that the GLA-induced DA release did not involve the DAT. These results show that GLA-induced striatal DA release is probably mediated by an exocytotic-, Ca(++)-, action potential-dependent mechanism, being independent of DAT.
本工作的目的是评估草铵膦（GLA），一种与谷氨酸结构相关的氨基酸，对使用 HPLC-EC 耦联脑微透析的大鼠纹状体中多巴胺（DA）释放的体内影响。纹状体内给予 GLA 可显著浓度依赖性地增加 DA 水平。可以提出至少两种机制来解释这些增加：GLA 可能诱导突触小泡中的 DA 释放，或者产生对 DA 转运蛋白（DAT）的抑制。因此，我们在无 Ca(++)条件下以及用利血平和 TTX 预处理后研究了 GLA 的作用。观察到，无 Ca(++)Ringer、利血平和 TTX 的预处理显著降低了 GLA 诱导的 DA 释放。GLA 和诺米芬辛的共输注表明，GLA 诱导的 DA 释放不涉及 DAT。这些结果表明，GLA 诱导的纹状体 DA 释放可能是通过胞吐作用、Ca(++)、动作电位依赖性机制介导的，而与 DAT 无关。
