Mapping the location of the growth hormone secretagogue receptor in the mouse brain using a novel fluorescent ligand

BARRILE, FRANCO; TOLOSA, MARÍA JOSÉ; REYNALDO, MIRTA; DE FRANCESCO, PABLO NICOLÁS; CABRAL, AGUSTINA; PERELLO, MARIO; CORNEJO, MARÍA PAULA; GARCÍA ROMERO, GUADALUPE

https://san2020.saneurociencias.org.ar/posters/mapping-the-location-of-the-growth-hormone-secretagogue-receptor-in-the-mouse-brain-using-a-novel-fluorescent-ligand/

Congreso; XXXV Reunión Anual SAN 2020; 2020

Sociedad Argentina de Investigación en Neurociencias

The growth hormone secretagogue receptor (GHSR) is aG-protein coupled receptor highly expressed in the brain that modulates avariety of metabolic, endocrine, autonomic and behavioural functions. GHSR isactivated by ghrelin and blocked by a liver-derived hormone named Liver-expressedantimicrobial peptide 2 (LEAP2). Here, we developed a novel fluorescent GHSRligand based on the N-terminal sequence of LEAP2, hereafter called FLEAP2, andassessed its capability to label GHSR in the mouse brain. We found that FLEAP2impaired ghrelin-induced food intake in the same fashion that native LEAP2 whenadministrated intracerebroventricularly (ICV) in mice. Furthermore, in miceICV-injected with FLEAP2, we found that brain regions with the highestfluorescent signal were the CA3 region of the hippocampus and the arcuatenucleus of the hypothalamus. In order to test the specificity of FLEAP2 towardsGHSR labelling, we ICV injected mice with FLEAP2 after ICV pre-treatment withvehicle, native LEAP2 or ghrelin. We analysed the level of fluorescent signalin the arcuate nucleus of these mice, as it is the brain region with highestGHSR expression, and mice pretreated with native LEAP2 orghrelin had lower fluorescent signal than vehicle pretreated mice. Thus,current data indicate that FLEAP2 specifically binds to GHSR and is anappropriate tool to study LEAP2 binding and function in the mouse brain.