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

FRANCO BARRILE; NICOLÁS DE FRANCESCO; PAULA CORNEJO; MARÍA JOSÉ TOLOSA; AGUSTINA CABRAL ; GUADALUPE GARCIA ROMERO; MIRTA REYNALDO; MARIO PERELLÓ

Congreso; REunion Anual SAN; 2020

The growth hormone secretagogue receptor (GHSR)is aG-protein coupled receptor highly expressed in the brain and that modulates avariety of metabolic, endocrine, autonomic and behavioural functions. GHSR isactivated by ghrelin and blocked by a liver-derived hormonenamed Liver-expressedantimicrobial peptide 2 (LEAP2). Here, we developeda novel fluorescent GHSRligand based on the N-terminal sequence of LEAP2, hereafter called FLEAP2, andassess its capability to label GHSR in the mouse brain. We found that FLEAP2inhibited ghrelin-induced food intake when administratedintracerebroventricularly (ICV) in mice, in the same fashion thatnative LEAP2.Inmice ICV-injected with FLEAP2, we found that the regions with highestfluorescent signal were the CA3 region of the hippocampus and the arcuatenucleus of the hypothalamus. In order to tests the specificity of FLEAP2labelling in vivowe pretreated micewith vehicle, native LEAP2 or ghrelin ICV, and afterwards with FLEAP2. Then weanalysed fluorescent signal in the arcuate nucleus, a brain region with highGHSR expression. Mice pretreated with native LEAP2 or ghrelin had lowerfluorescent signal than vehicle pretreated mice. Thus, current data indicatethat FLEAP2 is an appropriate tool to study LEAP2 binding and function on micebrain regions.