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AuthorAguggia, Julieta
AuthorFernandez, Gimena
AuthorCassano, Daniela
AuthorMustafá,, Emilio R.
AuthorRodríguez, Silvia S.
AuthorCantel, Sonia
AuthorFehrentz, Jean-Alain
AuthorRaingo, Jesica
AuthorSchiöth, Helgi B.
AuthorHabib, Abdella M.
AuthorDe Francesco, Pablo N.
AuthorPerello, Mario
Available date2025-03-03T07:10:07Z
Publication Date2024
Publication NameEndocrinology
ResourceScopus
Identifierhttp://dx.doi.org/10.1210/endocr/bqae160
ISSN19457170
URIhttp://hdl.handle.net/10576/63418
AbstractThe GH secretagogue receptor (GHSR) and the glucagon-like peptide-1 receptor (GLP-1R) are G protein-coupled receptors with critical, yet opposite, roles in regulating energy balance. Interestingly, these receptors are expressed in overlapping brain regions. However, the extent to which they target the same neurons and engage in molecular crosstalk remains unclear. To explore the potential colocalization of GHSR and GLP-1R in specific neurons, we performed detailed mapping of cells positive for both receptors using GHSR-eGFP reporter mice or wild-type mice infused with fluorescent ghrelin, alongside an anti-GLP-1R antibody. We found that GHSR+ and GLP-1R+ cells are largely segregated in the mouse brain. The highest overlap was observed in the hypothalamic arcuate nucleus, where 15% to 20% of GHSR+ cells were also GLP-1R+ cells. Additionally, we examined RNA-sequencing datasets from mouse and human brains to assess the fraction and distribution of neurons expressing both receptors, finding that double-positive Ghsr+/Glp1r+ cells are highly segregated, with a small subset of double-positive Ghsr+/Glp1r+ cells representing <10% of all Ghsr+ or Glp1r+ cells, primarily enriched in the hypothalamus. Furthermore, we conducted functional studies using patch-clamp recordings in a heterologous expression system to assess potential crosstalk in regulating presynaptic calcium channels. We provide the first evidence that liraglutide-evoked GLP-1R activity inhibits presynaptic channels, and that the presence of one GPCR attenuates the inhibitory effects of ligand-evoked activity mediated by the other on presynaptic calcium channels. In conclusion, while GHSR and GLP-1R can engage in molecular crosstalk, they are largely segregated across most neuronal types within the brain.
Languageen
PublisherOxford University Press
Subjectarcuate nucleus
calcium channels
ghrelin
GLP-1
TitleSelective Colocalization of GHSR and GLP-1R in a Subset of Hypothalamic Neurons and Their Functional Interaction
TypeArticle
Issue Number1
Volume Number166
dc.accessType Full Text


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