Involvement of adenosine A1 and A2A receptors on guanosine-mediated anti-tremor effects in reserpinized mice

• Published in: Purinergic signalling 2020-09, Vol.16 (3), p.379-387
• Main Authors: Massari, C. M., Constantino, L. C., Marques, N. F., Binder, L. B., Valle-León, M., López-Cano, M., Fernández-Dueñas, V., Ciruela, F., Tasca, C. I.
• Format: Article
• Language: English
• Subjects: Adenosine; Adenosine A2A receptors; Animal models; Antioxidants; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell membranes; Human Physiology; Jaw; Movement disorders; Neostriatum; Neurodegenerative diseases; Neurosciences; Original; Original Article; Parkinson's disease; Pharmacology/Toxicology; Reactive oxygen species; Reserpine; Tremor
• ISSN: 1573-9538; 1573-9546
• DOI: 10.1007/s11302-020-09716-z

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 A 1 and A 2A receptors (A 1 R and A 2A R) 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 2A R 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 2A R, thus suggesting an A 2A R-independent mechanism of GUO-mediated effects. Conversely, the administration of DPCPX (0.75 mg/kg), an A 1 R 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 A 1 R dependent but A 2A R independent, thus suggesting a differential participation of adenosine receptors in GUO-mediated effects.