Development of a novel fluorescent ligand of growth hormone secretagogue receptor based on the N-Terminal Leap2 region

Publication date: Available online 6 September 2019Source: Molecular and Cellular EndocrinologyAuthor(s): Franco Barrile, Céline M'Kadmi, Pablo N. De Francesco, Agustina Cabral, Guadalupe García Romero, Emilio R. Mustafá, Sonia Cantel, Marjorie Damian, Sophie Mary, Séverine Denoyelle, Jean-Louis Banères, Jacky Marie, Jesica Raingo, Jean-Alain Fehrentz, Mario PerellóAbstractLiver-expressed antimicrobial peptide 2 (LEAP2) was recently recognized as an endogenous ligand for the growth hormone secretagogue receptor (GHSR), which also is a receptor for the hormone ghrelin. LEAP2 blocks ghrelin-induced activation of GHSR and inhibits GHSR constitutive activity. Since fluorescence-based imaging and pharmacological analyses to investigate the biology of GHSR require reliable probes, we developed a novel fluorescent GHSR ligand based on the N-terminal LEAP2 sequence, hereafter named F-LEAP2. In vitro, F-LEAP2 displayed binding affinity and inverse agonism to GHSR similar to LEAP2. In a heterologous expression system, F-LEAP2 labeling was specifically observed in the surface of GHSR-expressing cells, in contrast to fluorescent ghrelin labeling that was mainly observed inside the GHSR-expressing cells. In mice, centrally-injected F-LEAP2 reduced ghrelin-induced food intake, in a similar fashion to LEAP2, and specifically labeled cells in GHSR-expressing brain areas. Thus, F-LEAP2 represents a valuable tool to study the biology of GHSR in vitro and in vivo.
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research