GHRP-6Growth Hormone Releasing Peptide-6 — Research Reference by QSC Peptides

GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH₂) was the first synthetic GH releasing peptide developed, derived from the structure of met-enkephalin in the 1970s–80s. It acts as a hexapeptide GHSR-1a agonist, stimulating GH release via Gq → PLC → IP3 → Ca²⁺ → GH exocytosis on pituitary somatotrophs.

Unlike Ipamorelin (which is selective) or GHRP-2 (which primarily elevates GH), GHRP-6 strongly activates appetite-stimulating ghrelin signaling pathways in the hypothalamic arcuate nucleus — specifically NPY/AgRP neurons. This dual GH + appetite stimulation profile makes GHRP-6 the compound of choice for studying full ghrelin receptor biology.

Historical Significance

GHRP-6 was instrumental in the discovery of the ghrelin receptor (GHSR-1a), which was initially an orphan GPCR. The identification that GHRP-6 bound this receptor preceded the discovery of its endogenous ligand ghrelin by nearly two decades, establishing GHRP-6 as a foundational tool in GH secretagogue receptor pharmacology.