Parkinson’s disease (PD) signs and symptoms regularly include tremor. Interestingly, the nucleoside guanosine (GUO) has already proven to be effective in reducing reserpine-induced tremulous jaw movements (TJMs) in rodent models, thus becoming a promising antiparkinsonian drug. Here, we aimed at revealing the mechanism behind GUO antiparkinsonian efficacy by assessing the role of adenosine A₁ and A_2A receptors (A₁R and A_2AR) on GUO-mediated anti-tremor effects in the reserpinized mouse model of PD. Reserpinized mice showed elevated reactive oxygen species (ROS) production and cellular membrane damage in striatal slices assessed ex vivo and GUO treatment reversed ROS production. Interestingly, while the simultaneous administration of sub-effective doses of GUO (5 mg/kg) and SCH58261 (0.01 mg/kg), an A_2AR antagonist, precluded reserpine-induced TJMs, these were ineffective on reverting ROS production in ex vivo experiments. Importantly, GUO was able to reduce TJM and ROS production in reserpinized mouse lacking the A_2AR, thus suggesting an A_2AR-independent mechanism of GUO-mediated effects. Conversely, the administration of DPCPX (0.75 mg/kg), an A₁R antagonist, completely abolished both GUO-mediated anti-tremor effects and blockade of ROS production. Overall, these results indicated that GUO anti-tremor and antioxidant effects in reserpinized mice were A₁R dependent but A_2AR independent, thus suggesting a differential participation of adenosine receptors in GUO-mediated effects.

帕金森病 (PD) 的体征和症状通常包括震颤。有趣的是，核苷鸟苷 (GUO) 已被证明可有效减少啮齿动物模型中利血平引起的震颤下颌运动 (TJMs)，从而成为一种有前途的抗帕金森病药物。在这里，我们旨在通过评估腺苷 A ₁和 A _2A受体（A ₁ R 和 A _2AR) 在 PD 的 reserpinized 小鼠模型中 GUO 介导的抗震颤作用。Reserpinized 小鼠表现出升高的活性氧 (ROS) 产生和纹状体切片中的细胞膜损伤，经体外评估和 GUO 治疗逆转了 ROS 产生。有趣的是，亚有效剂量郭（5毫克/千克）和SCH58261（0.01毫克/千克），一个A的同时给药_2A ř拮抗剂，排除了利血平引起TJMs，这些是无效的上恢复ROS产生在体外实验。重要的是，GUO 能够减少缺乏 A _2A R 的再血氨化小鼠中 TJM 和 ROS 的产生，从而表明GUO 介导的效应的 A _2A R 独立机制。相反，给予 DPCPX (0.75 mg/kg)，A ₁R 拮抗剂，完全消除了 GUO 介导的抗震颤作用和对 ROS 产生的阻断。总体而言，这些结果表明 GUO 抗震颤和抗氧化作用在 reserpinized 小鼠中是 A ₁ R 依赖的但 A _2A R 独立，因此表明腺苷受体在 GUO 介导的作用中的不同参与。