Identity a synthetic hexapeptide (6 amino acids, with two D-residues for protease resistance; < 40 aa → peptide), a ghrelin-receptor (GHS-R1a) agonist. Half-life ~2.5 h. ## Development & history - GHRP-6 was the first growth-hormone-releasing peptide, synthesised and characterised by Cyril Y. Bowers at Tulane University in 1984 (Bowers, Momany, Reynolds, Hong). It emerged from systematic modification of met-enkephalin analogs — Bowers noticed some enkephalin derivatives had unexpected GH-releasing activity unrelated to opioid receptors. Every later GH secretagogue (GHRP-2, hexarelin, ipamorelin, the oral MK-677) descends from it.
- The "fake key": GHRP-6 activated a receptor no one had identified. Characterising it led first to the cloning of the GH-secretagogue receptor (GHS-R1a) in 1996 (Howard et al.), and then — hunting for that receptor's natural ligand — to the discovery of ghrelin in 1999 (Kojima & Kangawa, Osaka), found surprisingly in the stomach. GHRP-6 thus opened up the entire ghrelin / gut-brain hunger-and-GH axis. Its strong appetite effect, first dismissed as a side effect, turned out to be the crucial clue (ghrelin signals both hunger and GH). ## Mechanism (as proposed) GHRP-6 binds GHS-R1a on two populations — pituitary somatotrophs (driving GH release via the Gq-PLC-calcium pathway) and hypothalamic arcuate-nucleus orexigenic neurons (driving hunger). The same receptor drives both GH and appetite, exactly as endogenous ghrelin does physiologically. Its non-selectivity comes from additional HPA-axis (cortisol) and prolactin activation, plus gastric-motility effects.