GHRP-2 – Potent Ghrelin Receptor Agonist & Growth Hormone Secretagogue

Chemical Identity

Chemical Name: Growth Hormone Releasing Peptide-2 Acetate
Molecular Formula: C₄₅H₅₅N₉O₆
Molecular Weight: ~817.0 Da
CAS Number: 158861-67-7
Sequence: D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH₂
Structure Type: Synthetic hexapeptide; high-affinity agonist of GHSR-1a (ghrelin receptor)

Pharmacological Classification

GHRP-2 is a **second-generation growth hormone secretagogue (GHS)** that potently activates the **GHSR-1a (ghrelin receptor)** to stimulate robust, pulsatile growth hormone release. It is structurally related to GHRP-6 but exhibits higher GH-releasing potency and receptor affinity, with a reduced orexigenic profile.

Mechanism of Action

• GHSR-1a Binding: Activates G_q and G_i/o-linked pathways in pituitary somatotrophs and hypothalamic neurons.
• GH Pulse Amplification: Promotes rapid GH secretion, especially when co-administered with GHRH analogs.
• Minimal Orexigenic Effect: Unlike GHRP-6, GHRP-2 has reduced appetite stimulation, making it preferable in contexts where GH elevation is desired without hyperphagia.

β-Arrestin Recruitment

GHRP-2 demonstrates **moderate β-arrestin recruitment**, higher than Ipamorelin but generally lower than ghrelin itself. This facilitates potent receptor activation with some potential for desensitization over prolonged use. It exhibits less receptor bias than Ipamorelin, but more than GHRP-6.

GHSR-1a Ligand Bias Comparison

Ligand	GH Release	β-Arrestin Recruitment	Desensitization Risk
Ghrelin	Strong	High	High
GHRP-6	Strong	Moderate–High	Moderate
GHRP-2	Very Strong	Moderate	Moderate
Ipamorelin	Moderate–Strong	Low	Low

Pharmacokinetics (Non-Dosing)

• Half-Life: ~30 minutes (short-acting)
• Onset: Rapid GH pulse within ~15 minutes of administration
• Clearance: Renal and enzymatic hydrolysis via peptidases

Biological Effects

Rapidly increases circulating GH and IGF-1, promotes muscle preservation, and accelerates post-injury recovery in rodent models. Unlike GHRP-6, it exhibits only mild orexigenic effects. Some studies report transient elevations in prolactin or ACTH under certain dosing regimens.

Stability and Storage

• Form: Lyophilized peptide acetate salt
• Solubility: Water, dilute acetic acid, 0.01 M HCl
• Storage: –20°C; dry, light-protected conditions
• Reconstitution pH: 4.5–6.0 recommended for optimal peptide integrity

References

1. Smith RG, et al. Endocr Rev. 1997;18(5):621–645.
2. Muller EE, Locatelli V. Endocr Dev. 2010;17:9–21.
3. van der Lely AJ, et al. Eur J Endocrinol. 2004;151(Suppl 1):S1–S9.
4. Camargos ST, et al. J Pediatr Endocrinol Metab. 2010;23(11):1133–1142.