Cannabinoid regulation of angiotensin II-induced calcium signaling in striatal neurons
Abstract Calcium ion (Ca2+) homeostasis is crucial for neuron function and neurotransmission. This study focused on the actions mediated by the CB1 receptor (CB1R), the most abundant G protein-coupled receptor (GPCR) in central nervous system (CNS) neurons, over by the AT1R, which is one of the few...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-11-01
|
| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-024-00827-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846165379141861376 |
|---|---|
| author | Rafael Rivas-Santisteban Ana Muñoz Jaume Lillo Iu Raïch Ana I. Rodríguez-Pérez Gemma Navarro José L. Labandeira-García Rafael Franco |
| author_facet | Rafael Rivas-Santisteban Ana Muñoz Jaume Lillo Iu Raïch Ana I. Rodríguez-Pérez Gemma Navarro José L. Labandeira-García Rafael Franco |
| author_sort | Rafael Rivas-Santisteban |
| collection | DOAJ |
| description | Abstract Calcium ion (Ca2+) homeostasis is crucial for neuron function and neurotransmission. This study focused on the actions mediated by the CB1 receptor (CB1R), the most abundant G protein-coupled receptor (GPCR) in central nervous system (CNS) neurons, over by the AT1R, which is one of the few G protein-coupled CNS receptors able to regulate cytoplasmic Ca2+ levels. A functional interaction suggesting a direct association between these receptors was detected. AT1-CB1 receptor heteromers (AT1CB1Hets) were identified in HEK-293T cells by bioluminescence resonance energy transfer (BRET2). Functional interactions within the AT1-CB1 complex and their potential relevance in Parkinson’s disease (PD) were assessed. In situ proximity ligation assays (PLA) identified AT1CB1Hets in neurons, in which an important finding was that Ca2+ level increase upon AT1R activation was reduced in the presence of cannabinoids acting on CB1Rs. AT1CB1Het expression was quantified in samples from the 6-hydroxydopamine (6-OHDA) hemilesioned rat model of PD in which a lower expression of AT1CB1Hets was observed in striatal neurons from lesioned animals (versus non-lesioned). AT1CB1Het expression changed depending on both the lesion and the consequences of levodopa administration, i.e., dyskinesias versus lack of involuntary movements. A partial recovery in AT1CB1Het expression was detected in lesioned animals that developed levodopa-induced dyskinesias. These findings support the existence of a compensatory mechanism mediated by AT1CB1Hets that modulates susceptibility to levodopa-induced dyskinesias in PD. Therefore, cannabinoids may be useful in reducing calcium dyshomeostasis in dyskinesia. |
| format | Article |
| id | doaj-art-13cd6a6a7aa44df2aecc5b45a642df9e |
| institution | Kabale University |
| issn | 2373-8057 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj-art-13cd6a6a7aa44df2aecc5b45a642df9e2024-11-17T12:16:18ZengNature Portfolionpj Parkinson's Disease2373-80572024-11-0110111410.1038/s41531-024-00827-7Cannabinoid regulation of angiotensin II-induced calcium signaling in striatal neuronsRafael Rivas-Santisteban0Ana Muñoz1Jaume Lillo2Iu Raïch3Ana I. Rodríguez-Pérez4Gemma Navarro5José L. Labandeira-García6Rafael Franco7Laboratory of Computational Medicine, Biostatistics Unit, Faculty of Medicine, Autonomous University of Barcelona, Campus BellaterraNetwork Center for Biomedical Research in Neurodegenerative Diseases, CiberNed, Spanish National Health Institute Carlos iiiNetwork Center for Biomedical Research in Neurodegenerative Diseases, CiberNed, Spanish National Health Institute Carlos iiiNetwork Center for Biomedical Research in Neurodegenerative Diseases, CiberNed, Spanish National Health Institute Carlos iiiNetwork Center for Biomedical Research in Neurodegenerative Diseases, CiberNed, Spanish National Health Institute Carlos iiiNetwork Center for Biomedical Research in Neurodegenerative Diseases, CiberNed, Spanish National Health Institute Carlos iiiNetwork Center for Biomedical Research in Neurodegenerative Diseases, CiberNed, Spanish National Health Institute Carlos iiiNetwork Center for Biomedical Research in Neurodegenerative Diseases, CiberNed, Spanish National Health Institute Carlos iiiAbstract Calcium ion (Ca2+) homeostasis is crucial for neuron function and neurotransmission. This study focused on the actions mediated by the CB1 receptor (CB1R), the most abundant G protein-coupled receptor (GPCR) in central nervous system (CNS) neurons, over by the AT1R, which is one of the few G protein-coupled CNS receptors able to regulate cytoplasmic Ca2+ levels. A functional interaction suggesting a direct association between these receptors was detected. AT1-CB1 receptor heteromers (AT1CB1Hets) were identified in HEK-293T cells by bioluminescence resonance energy transfer (BRET2). Functional interactions within the AT1-CB1 complex and their potential relevance in Parkinson’s disease (PD) were assessed. In situ proximity ligation assays (PLA) identified AT1CB1Hets in neurons, in which an important finding was that Ca2+ level increase upon AT1R activation was reduced in the presence of cannabinoids acting on CB1Rs. AT1CB1Het expression was quantified in samples from the 6-hydroxydopamine (6-OHDA) hemilesioned rat model of PD in which a lower expression of AT1CB1Hets was observed in striatal neurons from lesioned animals (versus non-lesioned). AT1CB1Het expression changed depending on both the lesion and the consequences of levodopa administration, i.e., dyskinesias versus lack of involuntary movements. A partial recovery in AT1CB1Het expression was detected in lesioned animals that developed levodopa-induced dyskinesias. These findings support the existence of a compensatory mechanism mediated by AT1CB1Hets that modulates susceptibility to levodopa-induced dyskinesias in PD. Therefore, cannabinoids may be useful in reducing calcium dyshomeostasis in dyskinesia.https://doi.org/10.1038/s41531-024-00827-7 |
| spellingShingle | Rafael Rivas-Santisteban Ana Muñoz Jaume Lillo Iu Raïch Ana I. Rodríguez-Pérez Gemma Navarro José L. Labandeira-García Rafael Franco Cannabinoid regulation of angiotensin II-induced calcium signaling in striatal neurons npj Parkinson's Disease |
| title | Cannabinoid regulation of angiotensin II-induced calcium signaling in striatal neurons |
| title_full | Cannabinoid regulation of angiotensin II-induced calcium signaling in striatal neurons |
| title_fullStr | Cannabinoid regulation of angiotensin II-induced calcium signaling in striatal neurons |
| title_full_unstemmed | Cannabinoid regulation of angiotensin II-induced calcium signaling in striatal neurons |
| title_short | Cannabinoid regulation of angiotensin II-induced calcium signaling in striatal neurons |
| title_sort | cannabinoid regulation of angiotensin ii induced calcium signaling in striatal neurons |
| url | https://doi.org/10.1038/s41531-024-00827-7 |
| work_keys_str_mv | AT rafaelrivassantisteban cannabinoidregulationofangiotensiniiinducedcalciumsignalinginstriatalneurons AT anamunoz cannabinoidregulationofangiotensiniiinducedcalciumsignalinginstriatalneurons AT jaumelillo cannabinoidregulationofangiotensiniiinducedcalciumsignalinginstriatalneurons AT iuraich cannabinoidregulationofangiotensiniiinducedcalciumsignalinginstriatalneurons AT anairodriguezperez cannabinoidregulationofangiotensiniiinducedcalciumsignalinginstriatalneurons AT gemmanavarro cannabinoidregulationofangiotensiniiinducedcalciumsignalinginstriatalneurons AT josellabandeiragarcia cannabinoidregulationofangiotensiniiinducedcalciumsignalinginstriatalneurons AT rafaelfranco cannabinoidregulationofangiotensiniiinducedcalciumsignalinginstriatalneurons |