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Title: | 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, Cristina Rivas‐Santisteban, Rafael Casals i Farré, Núria Navarro Brugal, Gemma Franco Fernández, Rafael |
Keywords: | Anorèxia Marihuana Farmacologia Obesitat Dieta Anorexia Marijuana Pharmacology Obesity Diet |
Issue Date: | 19-Aug-2021 |
Publisher: | MDPI |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/ijms22168928 |
It is part of: | International Journal of Molecular Sciences, 2021, vol. 22, num. 16, p. 1-17 |
URI: | http://hdl.handle.net/2445/181307 |
Related resource: | https://doi.org/10.3390/ijms22168928 |
ISSN: | 1661-6596 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) Articles publicats en revistes (Bioquímica i Fisiologia) |
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