Adenosine A1 and A2A receptors are involved on guanosine protective effects against oxidative burst and mitochondrial dysfunction induced by 6-OHDA in striatal slices
| Autor: | Leandra C. Constantino, Carla I. Tasca, Caio M. Massari |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Agonist medicine.drug_class Antagonist Guanosine Cell Biology Pharmacology Adenosine Adenosine receptor 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine nervous system Mechanism of action chemistry CCPA medicine medicine.symptom Receptor Molecular Biology 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Purinergic Signalling. 17:247-254 |
| ISSN: | 1573-9546 1573-9538 |
| Popis: | 6-Hydroxydopamine (6-OHDA) is the most used toxin in experimental Parkinson's disease (PD) models. 6-OHDA shows high affinity for the dopamine transporter and once inside the neuron, it accumulates and undergoes non-enzymatic auto-oxidation, promoting reactive oxygen species (ROS) formation and selective damage of catecholaminergic neurons. In this way, our group has established a 6-OHDA in vitro protocol with rat striatal slices as a rapid and effective model for screening of new drugs with protective effects against PD. We have shown that co-incubation with guanosine (GUO, 100 μM) prevented the 6-OHDA-induced damage in striatal slices. As the exact GUO mechanism of action remains unknown, the aim of this study was to investigate if adenosine A1 (A1R) and/or A2A receptors (A2AR) are involved on GUO protective effects on striatal slices. Pre-incubation with DPCPX, an A1R antagonist prevented guanosine effects on 6-OHDA-induced ROS formation and mitochondrial membrane potential depolarization, while CCPA, an A1R agonist, did not alter GUO effects. Regarding A2AR, the antagonist SCH58261 had similar protective effect as GUO in ROS formation and mitochondrial membrane potential. Additionally, SCH58261 did not affect GUO protective effects. The A2AR agonist CGS21680, although, completely blocked GUO effects. Finally, the A1R antagonist DPCPX, and the A2AR agonist CGS21680 also abolished the preventive guanosine effect on 6-OHDA-induced ATP levels decrease. These results reinforce previous evidence for a putative interaction of GUO with A1R-A2AR heteromer as its molecular target and clearly indicate a dependence on adenosine receptors modulation to GUO protective effect. |
| Databáze: | OpenAIRE |
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