Gomes Catarina A R V, Vaz Sandra H, Ribeiro Joaquim A, Sebastião Ana M
Institute of Pharmacology and Neurosciences, Faculty of Medicine and Institute of Molecular Medicine, University of Lisbon, Portugal.
Brain Res. 2006 Oct 3;1113(1):129-36. doi: 10.1016/j.brainres.2006.07.025. Epub 2006 Aug 28.
Both glial cell line-derived neurotrophic factor (GDNF) and adenosine influence dopaminergic function in the striatum. We now evaluated the GDNF effect on dopamine release from rat striatal nerve endings and if this effect of GDNF is modulated by adenosine A(2A) receptors. Dopamine release was evoked twice (S(1) and S(2)); GDNF was added before S(2) and drugs used to modify GDNF actions were present during both stimulation periods. The effect of GDNF was taken as the change in the S(2)/S(1) ratio in the absence and in the presence of GDNF in the same experimental conditions. GDNF (3-30 ng/ml) increased dopamine release from K(+) (20 mM, 2 min) stimulated synaptosomes and electrically (2 Hz, 2 min) stimulated striatal slices, an effect dependent upon tonic adenosine A(2A) receptor activation, since it was blocked by the A(2A) receptor antagonist, SCH 58261 (50 nM). Activation of A(2A) receptors with CGS 21680 (10 nM) potentiated the effect of GDNF in synaptosomes. CGS 21680 also potentiated the effect of GDNF in striatal slices, providing that GABAergic transmission was inhibited; if not, the action of GDNF was attenuated by CGS 21680. Blockade of GABAergic transmission per se increased dopamine release, but attenuated the effect of GDNF upon dopamine release in slices. The results suggest that GDNF enhances dopamine release by acting presynaptically at the striatum, an action that requires adenosine A(2A) receptor activity. Furthermore, in striatal slices, the action of GDNF as well as its modulation by adenosine A(2A) receptor activation appears to be also under control of GABAergic transmission.
胶质细胞源性神经营养因子（GDNF）和腺苷均会影响纹状体中的多巴胺能功能。我们现在评估了GDNF对大鼠纹状体神经末梢多巴胺释放的影响，以及GDNF的这种作用是否受腺苷A(2A)受体的调节。多巴胺释放被诱发两次（S(1)和S(2)）；在S(2)之前加入GDNF，并且在两个刺激期均使用用于改变GDNF作用的药物。在相同实验条件下，将GDNF的作用视为有无GDNF时S(2)/S(1)比值的变化。GDNF（3 - 30 ng/ml）增加了K(+)（20 mM，2分钟）刺激的突触体以及电刺激（2 Hz，2分钟）的纹状体切片中的多巴胺释放，这种作用依赖于持续性腺苷A(2A)受体激活，因为它被A(2A)受体拮抗剂SCH 58261（50 nM）阻断。用CGS 21680（10 nM）激活A(2A)受体可增强GDNF在突触体中的作用。CGS 21680也增强了GDNF在纹状体切片中的作用，前提是GABA能传递被抑制；如果未被抑制，GDNF的作用会被CGS 21680减弱。阻断GABA能传递本身会增加多巴胺释放，但会减弱GDNF对切片中多巴胺释放的作用。结果表明，GDNF通过在纹状体突触前发挥作用来增强多巴胺释放，这一作用需要腺苷A(2A)受体活性。此外，在纹状体切片中，GDNF的作用及其受腺苷A(2A)受体激活的调节似乎也受GABA能传递的控制。
