Involvement of adenosine A 1 and A 2A receptors on guanosine-mediated anti-tremor effects in reserpinized mice
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ORIGINAL ARTICLE
Involvement of adenosine A1 and A2A receptors on guanosine-mediated anti-tremor effects in reserpinized mice C. M. Massari 1,2 & L. C. Constantino 2,3 & N. F. Marques 1,2 & L. B. Binder 2,3 & M. Valle-León 4,5 & M. López-Cano 4,5 & V. Fernández-Dueñas 4,5 & F. Ciruela 4,5 & C. I. Tasca 1,2,3 Received: 24 April 2020 / Accepted: 16 July 2020 # Springer Nature B.V. 2020
Abstract 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 A2A receptors (A1R and A2AR) 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 A2AR antagonist, precluded reserpineinduced 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 A2AR, thus suggesting an A2AR-independent mechanism of GUOmediated effects. Conversely, the administration of DPCPX (0.75 mg/kg), an A1R antagonist, completely abolished both GUOmediated 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 A2AR independent, thus suggesting a differential participation of adenosine receptors in GUO-mediated effects. Keywords Guanosine . Tremor . Reserpine . Adenosine receptors
Introduction Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide. It is mainly characterized by the * C. I. Tasca [email protected] 1
Programa de Pós-graduação em Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Brazil
2
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Brazil
3
Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Brazil
4
Unitat de Farmacologia, Departament de Patologia i Terapèutica Experimental, Facultatde Medicina i Ciències de la Salut, IDIBELL, Universitat de Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain
5
Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
progressive loss of dopaminergic neurons within the nigrostriatal pathway, which leads to a debilitating motor dysfunction [1]. The cardinal motor symptoms of Parkinsonism include akinesia, bradykinesia, rigidity, and a resting tremor [1]. Tremor can be def
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