Cannabinoid regulation of angiotensin II-induced calcium signaling in striatal neurons
Rivas-Santisteban, Rafael (Universitat Autònoma de Barcelona)
Muñoz, Ana (Universidade de Santiago de Compostela)
Lillo, Jaume (Universitat de Barcelona. Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences)
Raïch, Iu (Universitat de Barcelona. Departament de Bioquímica i Fisiologia)
Rodríguez-Pérez, Ana I. (Universidade de Santiago de Compostela)
Navarro Brugal, Gemma (Universitat de Barcelona)
Labandeira-García, José Luis (Universidade de Santiago de Compostela)
Franco, Rafael (Universitat de Barcelona)

Data:	2024
Resum:	Calcium ion (Ca 2+) homeostasis is crucial for neuron function and neurotransmission. This study focused on the actions mediated by the CB receptor (CBR), the most abundant G protein-coupled receptor (GPCR) in central nervous system (CNS) neurons, over by the ATR, which is one of the few G protein-coupled CNS receptors able to regulate cytoplasmic Ca 2+ levels. A functional interaction suggesting a direct association between these receptors was detected. AT-CB receptor heteromers (ATCBHets) were identified in HEK-293T cells by bioluminescence resonance energy transfer (BRET 2). Functional interactions within the AT-CB complex and their potential relevance in Parkinson's disease (PD) were assessed. In situ proximity ligation assays (PLA) identified ATCBHets in neurons, in which an important finding was that Ca 2+ level increase upon ATR activation was reduced in the presence of cannabinoids acting on CBRs. ATCBHet expression was quantified in samples from the 6-hydroxydopamine (6-OHDA) hemilesioned rat model of PD in which a lower expression of ATCBHets was observed in striatal neurons from lesioned animals (versus non-lesioned). ATCBHet 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 ATCBHet expression was detected in lesioned animals that developed levodopa-induced dyskinesias. These findings support the existence of a compensatory mechanism mediated by ATCBHets that modulates susceptibility to levodopa-induced dyskinesias in PD. Therefore, cannabinoids may be useful in reducing calcium dyshomeostasis in dyskinesia.
Ajuts:	Agencia Estatal de Investigación PID2021-126600OB-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00304
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Parkinson's disease ; G protein-coupled receptors
Publicat a:	NPJ Parkinson's disease, Vol. 10 (november 2024) , ISSN 2373-8057

DOI: 10.1038/s41531-024-00827-7
PMID: 39548112

14 p, 3.9 MB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats