Pinna Annalisa, Corsi Claudia, Carta Anna Rosa, Valentini Valentina, Pedata Felicita, Morelli Micaela
CNR Center for Neuropharmacology, University of Cagliari, Cagliari, Italy
Eur J Pharmacol. 2002 Jun 20;446(1-3):75-82. doi: 10.1016/s0014-2999(02)01818-6.
Adenosine A(2A) receptor antagonists have been proposed as an effective therapy in the treatment of Parkinson's disease. To explore the possibility that dopamine denervation may produce modifications in adenosine A(2A) transmission, we measured the extracellular concentration of adenosine and adenosine A(2A) receptor mRNA in the striatum of rats infused unilaterally with 6-hydroxydopamine in the medial forebrain bundle. Fifteen days after 6-hydroxydopamine infusion, extracellular adenosine levels, measured by in vivo microdialysis, were significantly lower (-35%) in the dopamine-denervated striatum. At the time of the decrease in adenosine levels, an increase in striatal adenosine A(2A) receptor mRNA levels (+20%), measured by in situ hybridization, was observed. Modifications in adenosine A(2A) transmission, following nigrostriatal dopamine neuron degeneration, establish a potential neural basis for the effectiveness of adenosine A(2A) receptor antagonists in the treatment of Parkinson's disease.
腺苷A(2A)受体拮抗剂已被提议作为治疗帕金森病的一种有效疗法。为了探究多巴胺去神经支配是否会对腺苷A(2A)传递产生改变，我们测量了单侧在前脑内侧束注入6-羟基多巴胺的大鼠纹状体中腺苷的细胞外浓度以及腺苷A(2A)受体mRNA水平。在注入6-羟基多巴胺15天后，通过体内微透析测量发现，多巴胺去神经支配的纹状体中细胞外腺苷水平显著降低（-35%）。在腺苷水平下降时，通过原位杂交测量发现纹状体中腺苷A(2A)受体mRNA水平升高（+20%）。黑质纹状体多巴胺神经元变性后腺苷A(2A)传递的改变，为腺苷A(2A)受体拮抗剂治疗帕金森病的有效性奠定了潜在的神经基础。
