Identification of the ghrelin and cannabinoid CB2 receptor heteromer functionality and marked upregulation in striatal neurons from offspring of mice under a high-fat diet
Author
Lillo, Jaume
Lillo, Alejandro
Zafra, David A.
Miralpeix Monclús, Cristina
Rivas-Santisteban, Rafael
Casals i Farré, Núria
Navarro, Gemma
Franco, Rafael
Publication date
2021ISSN
1422-0067
Abstract
Cannabinoids have been reported as orexigenic, i.e., as promoting food intake that, among others, is controlled by the so-called “hunger” hormone, ghrelin. The aim of this paper was to look for functional and/or molecular interactions between ghrelin GHSR1a and cannabinoid CB2 receptors at the central nervous system (CNS) level. In a heterologous system we identified CB2-GHSR1a receptor complexes with a particular heteromer print consisting of impairment of CB2 receptor/Gi-mediated signaling. The blockade was due to allosteric interactions within the heteromeric complex as it was reverted by antagonists of the GHSR1a receptor. Cannabinoids acting on the CB2 receptor did not affect cytosolic increases of calcium ions induced by ghrelin acting on the GHSR1a receptor. In situ proximity ligation imaging assays confirmed the expression of CB2-GHSR1a receptor complexes in both heterologous cells and primary striatal neurons. We tested heteromer expression in neurons from offspring of high-fat-diet mouse mothers as they have more risk to be obese. Interestingly, there was a marked upregulation of those complexes in striatal neurons from siblings of pregnant female mice under a high-fat diet.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
61 - Medical sciences
Keywords
Orexigènic
Anorèxia
Marihuana
Fitocannabinoides
Receptors acoblats a proteïnes G
Farmacologia
Heteròmers receptors
Senyalització
Dieta rica en greixos
Obesitat
Orexigénico
Anorexia
Marihuana
Fitocannabinoides
Receptores acoplados a proteína G
Farmacología
Heterómeros receptores
Señalización
Dieta alta en grasas
Obesidad
Orexigenic
Anorexia
Marihuana
Phytocannabinoids
G protein-coupled receptors
Pharmacology
Receptor heteromers
Signaling
High-fat diet
Obesity
Pages
17
Publisher
MDPI
Collection
22; 16
Is part of
International Journal of Molecular Sciences
Citation
Lillo, Jaume; Lillo, Alejandro; Zafra, David A. [et al.]. Identification of the ghrelin and cannabinoid CB2 receptor heteromer functionality and marked upregulation in striatal neurons from offspring of mice under a high-fat diet. International Journal of Molecular Sciences, 2021, 22(16), 8928. Disponible en: <https://www.mdpi.com/1422-0067/22/16/8928>. Fecha de acceso: 20 sep. 2021. DOI: 10.3390/ijms22168928
This item appears in the following Collection(s)
- Ciències de la Salut [740]
Rights
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/