GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Characterization of the binding of MSH-B, HB-228, GHRP-6 and 153N-6 to the human melanocortin receptor subtypes.
Schiöth. H B HB; Muceniece. R R; Wikberg. J E JE
Key Findings
- GHRP‑6 binds weakly to MC1 and MC5 receptors, but not to MC3 or MC4.
- The modified peptide D‑Lys3‑GHRP‑6 binds all four melanocortin receptors with similar affinity.
- Other related peptides (Met‑enkephalin, GHRH, LHRH, somatostatin‑14) do not bind these receptors.
- Low‑affinity binding suggests GHRP‑6’s melanocortin activity is unlikely to be relevant at typical experimental concentrations.
Practical Outcomes
- For biohackers using GHRP‑6, the main action is still through the ghrelin receptor, not melanocortin pathways that affect appetite or pigmentation. There’s no need to adjust dosing to target MC receptors, and you shouldn’t expect extra benefits (or risks) from MC1/MC5 binding at normal doses.
Summary
The study shows that GHRP‑6 can stick to two of the melanocortin receptors (MC1 and MC5) but only very weakly, and a modified version (D‑Lys3‑GHRP‑6) sticks to all four receptors. Because the binding is so weak, the peptide probably doesn’t do anything useful through these receptors at the doses people normally use.
Abstract
We determined the binding affinities of the MSH analogues MSH-B, HP-228 and 153N-6 and of the enkephalin analogue GHRP-6 on a single eukaryotic cell line transiently expressing the human MC1, MC3, MC4 and MC5 receptors. Moreover, we tested the binding and cAMP response of MSH-B in comparison with alpha-MSH on murine B16 melanoma cells. Our results indicate that MSH-B has a potency similar to that of alpha-MSH and that these two peptides induce similar cAMP responses in murine B16 melanoma cells. HP-228 has its highest affinity for the MC1 receptor. For the other receptors, it has slightly higher affinity for the MC5 receptor than for the MC3 and MC4 receptors. 153N-6 was found to be selective for the MC1 receptor. GHRP-6 was found to bind to the MC1 and the MC5 receptors despite its low structural homology with alpha-MSH. [D-Lys3]GHRP-6 bound to all the four MC receptors with similar affinities. The structurally related Met-enkephalin and the functionally related GHRH, as well as LHRH and somatostatin-14 did not bind to these MC receptors. The low affinity of the GH-releasing/enkephalin peptides may indicate that they do not interact with the MC receptors at pharmacologically relevant concentrations.
Study Information
pubmed
1997
10.1016/s0143-4179(97)90002-0