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

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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 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 A2AR, thus suggesting an A2AR-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 A2AR independent, thus suggesting a differential participation of adenosine receptors in GUO-mediated effects.

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Funding

The research performed at the Universidade Federal de Santa Catarina was supported by the Brazilian funding agencies, CAPES (CAPES/PAJT), CNPq (INCT-EN for Excitotoxicity and Neuroprotection), and FAPESC (NENASC/PRONEX) to C.I.T. The research performed at the Universitat de Barcelona was supported by FEDER/Ministerio de Ciencia, Innovación y Universidades–Agencia Estatal de Investigación (SAF2017-87349-R) and ISCIII (PIE14/00034), the Catalan government (2017 SGR 1604), Fundació la Marató de TV3 (Grant 20152031), and FWO (SBO-140028) to F.C. Also, CAPES-PDSE (47/2017) provided doctoral fellowship to C.M.M. We thank LAMEB/UFSC team work for experimental support.

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Authors and Affiliations

  1. Programa de Pós-graduação em Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Brazil

    C. M. Massari, N. F. Marques & C. I. Tasca

  2. Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Brazil

    C. M. Massari, L. C. Constantino, N. F. Marques, L. B. Binder & C. I. Tasca

  3. Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Brazil

    L. C. Constantino, L. B. Binder & C. I. Tasca

  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

    M. Valle-León, M. López-Cano, V. Fernández-Dueñas & F. Ciruela

  5. Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain

    M. Valle-León, M. López-Cano, V. Fernández-Dueñas & F. Ciruela

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  1. C. M. Massari
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  2. L. C. Constantino
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  3. N. F. Marques
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  6. M. López-Cano
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  8. F. Ciruela
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  9. C. I. Tasca
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Correspondence to C. I. Tasca.

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The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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The study protocol was approved by the Ethical Committee on Animal Use and Care of the University of Barcelona (CEEA/UB) and Federal University of Santa Catarina (CEUA/UFSC, Protocol PP00955).

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Massari, C.M., Constantino, L.C., Marques, N.F. et al. Involvement of adenosine A1 and A2A receptors on guanosine-mediated anti-tremor effects in reserpinized mice. Purinergic Signalling 16, 379–387 (2020). https://doi.org/10.1007/s11302-020-09716-z

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