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Ghrelin receptor agonists and antagonists act on the growth hormone secretagogue receptor (GHSR). The receptor was cloned in 1996 from pituitary and hypothalamus as the target of synthetic growth hormone secretagogues. Its endogenous ligand, ghrelin, was identified in 1999 as an acylated stomach peptide that releases growth hormone. GHSR signaling links growth hormone release with appetite and energy balance, which makes the receptor a frequent subject in metabolism research. Anamorelin, capromorelin and ulimorelin are small-molecule GHSR agonists, and des-Gln14-Ghrelin is a natural ghrelin variant. PF-5190457 acts as an inverse agonist, while liver-expressed antimicrobial peptide 2 (LEAP-2) antagonizes the receptor.
des-Gln14-Ghrelin is a second endogenous ligand for the growth hormone secretagogue receptor. a). des-Gln14-ghrelin potently induces increases in [Ca2+]i in CHO-GHSR62 cells, with an EC50 of 2.4 nM.
