Boolean analysis shows a high proportion of dopamine D2 receptors interacting with adenosine A2A receptors in striatal medium spiny neurons of mouse and non-human primate models of Parkinson's disease
The antagonistic effect of adenosine on dopaminergic transmission in the basal ganglia indirect motor control pathway is mediated by dopamine D2 (D2R) and adenosine A2A (A2AR) receptors co-expressed on medium spiny striatal neurons. The pathway is unbalanced in Parkinson's disease (PD) and...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/217057 |
| Acceso en línea: | https://hdl.handle.net/2445/217057 |
| Access Level: | acceso abierto |
| Palabra clave: | Dopamina Receptors colinèrgics Adenosina Dopamine Acetylcholine receptors Adenosine |
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ES_4e34e7ddfa776b3c4e340215dfdbb973 |
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| oai_identifier_str |
oai:recercat.cat:2445/217057 |
| network_acronym_str |
ES |
| network_name_str |
España |
| spelling |
Boolean analysis shows a high proportion of dopamine D2 receptors interacting with adenosine A2A receptors in striatal medium spiny neurons of mouse and non-human primate models of Parkinson's disease Boolean analysis shows a high proportion of dopamine $D_2$ receptors interacting with adenosine $A_2A$ receptors in striatal medium spiny neurons of mouse and non-human primate models of Parkinson's disease Rivas‐Santisteban, Rafael Rico, Alberto José Muñoz, Ana Rodríguez Pérez, Ana I. Reyes Resina, Irene Navarro Brugal, Gemma Labandeira García, José L. Lanciego, José Luis Franco Fernández, Rafael Dopamina Receptors colinèrgics Adenosina Dopamine Acetylcholine receptors Adenosine The antagonistic effect of adenosine on dopaminergic transmission in the basal ganglia indirect motor control pathway is mediated by dopamine D2 (D2R) and adenosine A2A (A2AR) receptors co-expressed on medium spiny striatal neurons. The pathway is unbalanced in Parkinson's disease (PD) and an A2AR blocker has been approved for use with levodopa in the therapy of the disease. However, it is not known whether the therapy is acting on individually expressed receptors or in receptors forming A2A-D2 receptor heteromers, whose functionality is unique. For two proteins prone to interact, a very recently developed technique, MolBoolean, allows to determine the number of proteins that are either non-interacting or interacting. After checking the feasibility of the technique and reliability of data in transfected cells and in striatal primary neurons, the Boolean analysis of receptors in the striatum of rats and monkeys showed a high percentage of D2 receptors interacting with the adenosine receptor, while, on the contrary, a significant proportion of A2A receptors do not interact with dopamine receptors. The number of interacting receptors increased when rats and monkeys were lesioned to become a PD model. The use of a tracer of the indirect pathway in monkeys confirmed that the data was restricted to the population of striatal neurons projecting to the GPe. The results are not only relevant for being the first study quantifying individual versus interacting G protein-coupled receptors, but also for showing that the D2R in these specific neurons, in both control and PD animals, is under the control of the A2AR. The tight adenosine/dopamine receptor coupling suggest benefits of early antiparkinsonian treatment with adenosine receptor blockers. Elsevier https://hdl.handle.net/2445/217057 |
| title |
Boolean analysis shows a high proportion of dopamine D2 receptors interacting with adenosine A2A receptors in striatal medium spiny neurons of mouse and non-human primate models of Parkinson's disease |
| spellingShingle |
Boolean analysis shows a high proportion of dopamine D2 receptors interacting with adenosine A2A receptors in striatal medium spiny neurons of mouse and non-human primate models of Parkinson's disease Rivas‐Santisteban, Rafael Dopamina Receptors colinèrgics Adenosina Dopamine Acetylcholine receptors Adenosine |
| title_short |
Boolean analysis shows a high proportion of dopamine D2 receptors interacting with adenosine A2A receptors in striatal medium spiny neurons of mouse and non-human primate models of Parkinson's disease |
| title_full |
Boolean analysis shows a high proportion of dopamine D2 receptors interacting with adenosine A2A receptors in striatal medium spiny neurons of mouse and non-human primate models of Parkinson's disease |
| title_fullStr |
Boolean analysis shows a high proportion of dopamine D2 receptors interacting with adenosine A2A receptors in striatal medium spiny neurons of mouse and non-human primate models of Parkinson's disease |
| title_full_unstemmed |
Boolean analysis shows a high proportion of dopamine D2 receptors interacting with adenosine A2A receptors in striatal medium spiny neurons of mouse and non-human primate models of Parkinson's disease |
| title_sort |
Boolean analysis shows a high proportion of dopamine D2 receptors interacting with adenosine A2A receptors in striatal medium spiny neurons of mouse and non-human primate models of Parkinson's disease |
| author |
Rivas‐Santisteban, Rafael |
| author_facet |
Rivas‐Santisteban, Rafael Rico, Alberto José Muñoz, Ana Rodríguez Pérez, Ana I. Reyes Resina, Irene Navarro Brugal, Gemma Labandeira García, José L. Lanciego, José Luis Franco Fernández, Rafael |
| author_role |
author |
| author2 |
Rico, Alberto José Muñoz, Ana Rodríguez Pérez, Ana I. Reyes Resina, Irene Navarro Brugal, Gemma Labandeira García, José L. Lanciego, José Luis Franco Fernández, Rafael |
| author2_role |
author author author author author author author author |
| topic |
Dopamina Receptors colinèrgics Adenosina Dopamine Acetylcholine receptors Adenosine |
| topic_facet |
Dopamina Receptors colinèrgics Adenosina Dopamine Acetylcholine receptors Adenosine |
| description |
The antagonistic effect of adenosine on dopaminergic transmission in the basal ganglia indirect motor control pathway is mediated by dopamine D2 (D2R) and adenosine A2A (A2AR) receptors co-expressed on medium spiny striatal neurons. The pathway is unbalanced in Parkinson's disease (PD) and an A2AR blocker has been approved for use with levodopa in the therapy of the disease. However, it is not known whether the therapy is acting on individually expressed receptors or in receptors forming A2A-D2 receptor heteromers, whose functionality is unique. For two proteins prone to interact, a very recently developed technique, MolBoolean, allows to determine the number of proteins that are either non-interacting or interacting. After checking the feasibility of the technique and reliability of data in transfected cells and in striatal primary neurons, the Boolean analysis of receptors in the striatum of rats and monkeys showed a high percentage of D2 receptors interacting with the adenosine receptor, while, on the contrary, a significant proportion of A2A receptors do not interact with dopamine receptors. The number of interacting receptors increased when rats and monkeys were lesioned to become a PD model. The use of a tracer of the indirect pathway in monkeys confirmed that the data was restricted to the population of striatal neurons projecting to the GPe. The results are not only relevant for being the first study quantifying individual versus interacting G protein-coupled receptors, but also for showing that the D2R in these specific neurons, in both control and PD animals, is under the control of the A2AR. The tight adenosine/dopamine receptor coupling suggest benefits of early antiparkinsonian treatment with adenosine receptor blockers. |
| publishDate |
2023 |
| format |
article |
| status_str |
publishedVersion |
| url |
https://hdl.handle.net/2445/217057 |
| eu_rights_str_mv |
openAccess |
| publisher |
Elsevier |
| institution |
Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| collection |
Recercat. Dipósit de la Recerca de Catalunya |
| reponame_str |
Recercat. Dipósit de la Recerca de Catalunya |
| instname_str |
Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| _version_ |
1878434438831931392 |
| publishDateSort |
2023 |
| author_browse |
Franco Fernández, Rafael Labandeira García, José L. Lanciego, José Luis Muñoz, Ana Navarro Brugal, Gemma Reyes Resina, Irene Rico, Alberto José Rivas‐Santisteban, Rafael Rodríguez Pérez, Ana I. |
| publisherStr |
Elsevier |
| score |
6,9303427 |