GHRP-6 – Hexapeptide Ghrelin Receptor Agonist

Chemical Identity

Chemical Name: Growth Hormone Releasing Peptide-6 Acetate
Molecular Formula: C₄₆H₅₆N₁₂O₆
Molecular Weight: ~873.01 Da
CAS Number: 87616-84-0
Sequence: His-D-Trp-Ala-Trp-D-Phe-Lys-NH₂
Structure Type: Synthetic hexapeptide; ghrelin receptor (GHSR-1a) agonist

Pharmacological Classification

GHRP-6 is a first-generation **growth hormone secretagogue (GHS)** that binds and activates the **GHSR-1a (ghrelin receptor)**, stimulating pulsatile growth hormone (GH) release from anterior pituitary somatotrophs. It was among the earliest synthetic peptides developed to mimic the GH-releasing activity of ghrelin, with additional effects on appetite and metabolism.

Mechanism of Action

• GHSR-1a Activation: Binds to the growth hormone secretagogue receptor, triggering G_q and G_i/o-mediated intracellular signaling cascades.
• GH Release: Enhances pulsatile secretion of GH and synergizes with GHRH signaling pathways.
• Appetite Modulation: Promotes orexigenic effects by acting on hypothalamic neurons; mimics ghrelin in food intake models.

β-Arrestin Recruitment

GHRP-6 displays **moderate to high β-arrestin recruitment** at the GHSR-1a receptor, which contributes to receptor internalization and desensitization with chronic exposure. It is less biased than newer analogs like Ipamorelin, resulting in a stronger acute signal but reduced sustainability over time.

GHSR-1a Ligand Bias Comparison

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

Pharmacokinetics (Non-Dosing)

• Half-Life: ~20–30 minutes (short-acting)
• Bioavailability: Effective subcutaneously and intravenously
• Clearance: Primarily via proteolytic degradation and renal excretion

Biological Effects

GHRP-6 increases plasma GH and IGF-1, stimulates appetite, promotes lean mass development, and supports tissue repair in preclinical models. Unlike Ipamorelin, it may elevate prolactin and cortisol due to less selective receptor interactions at higher concentrations.

Stability and Storage

• Form: Lyophilized acetate salt
• Solubility: Water, 0.01 M HCl, saline, or acetic acid
• Storage: –20°C; protect from light and humidity
• Reconstitution: pH 4.5–5.5 recommended for solution stability

References

1. Smith RG, et al. Endocr Rev. 1997;18(5):621–645.
2. Chen HY, et al. Endocrinology. 1996;137(12):5242–5249.
3. Camargos ST, et al. J Pediatr Endocrinol Metab. 2010;23(11):1133–1142.
4. van der Lely AJ, et al. Eur J Endocrinol. 2004;151 Suppl 1:S1–S9.