GHRP-2

The overview

What is GHRP-2?

GHRP-2 is a synthetic hexapeptide that acts in vitro as a potent agonist of the growth hormone secretagogue receptor type 1a (GHS-R1a), the same class A G-protein-coupled receptor that binds endogenous ghrelin. In receptor-expressing cell systems and isolated anterior pituitary somatotroph preparations, GHS-R1a engagement couples predominantly to Gq/11, activating phospholipase C and generating inositol-1,4,5-trisphosphate (IP3) and diacylglycerol. This mobilizes Ca2+ from intracellular stores and activates protein kinase C, with reported contributions from the PKA/cyclic-AMP axis in some pituitary models. The net signaling output is depolarization and elevated intracellular Ca2+ that drives exocytosis of secretory granules. Pharmacological specificity is supported by blockade with the GHS-R1a antagonist [D-Lys3]-GHRP-6 in myocyte models. GHRP-2 binds at the conserved ligand-activation domain of GHS-R1a characterized after the receptor was cloned by Howard and colleagues. All statements describe in-vitro receptor binding and intracellular signal-transduction events only.

In the research

Where GHRP-2 shows up

The areas researchers focus on with GHRP-2 - and why it has the science community paying attention.

• GHS-R1a (ghrelin receptor) binding and agonist pharmacology in receptor-transfected cell lines
• Gq/11-phospholipase C / IP3-DAG / intracellular Ca2+ and PKC signal-transduction studies
• In-vitro anterior pituitary somatotroph secretory-granule exocytosis models
• Receptor-specificity profiling using [D-Lys3]-GHRP-6 antagonist blockade in cultured myocytes (C2C12)
• Comparative structure-activity studies within the growth hormone secretagogue / ghrelin-mimetic peptide class

By the numbers

The facts that matter

To the molecule

Molecular specifications

Sourced, not claimed

The science behind it

The peer-reviewed studies behind GHRP-2, linked so you can read them yourself.

1. Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, et al. (1996). A receptor in pituitary and hypothalamus that functions in growth hormone release Science.

   “A G protein-coupled receptor of the pituitary and hypothalamus was cloned and shown to be the target of the synthetic growth hormone secretagogues.”

   DOI ↗PubMed ↗
2. Yamamoto D, Ikeshita N, Matsubara T, Tasaki H, Herningtyas EH, Toda K, et al. (2008). GHRP-2, a GHS-R agonist, directly acts on myocytes to attenuate the dexamethasone-induced expressions of muscle-specific ubiquitin ligases, Atrogin-1 and MuRF1 Life Sciences.

   “The suppressive effect on the expressions of Atrogin-1 and MuRF1 by GHRP-2 was blocked by [D-Lys(3)]-GHRP-6, a GHS-R1a blocker.”

   DOI ↗PubMed ↗
3. Kageyama K, Kushibiki M, Hanada K, Sakihara S, Yasujima M, Suda T (2009). Growth hormone-releasing peptide-2 stimulates secretion and synthesis of adrenocorticotropic hormone in mouse pituitary Regulatory Peptides.

   “GHRP-2-induced ACTH release was regulated via both PKA and PKC pathways, while synthesis occurred only via the PKA pathway.”

   DOI ↗PubMed ↗
4. Pihoker C, Kearns GL, French D, Bowers CY (1998). Pharmacokinetics and pharmacodynamics of growth hormone-releasing peptide-2: a phase I study in children Journal of Clinical Endocrinology & Metabolism.

   “GHRP-2 produced a predictable and significant increase in plasma GH concentrations.”

   DOI ↗PubMed ↗
5. Bowers CY (1998). Growth hormone-releasing peptide (GHRP) Cellular and Molecular Life Sciences.

   “GHRPs are a class of growth hormone secretagogues that release GH by a mechanism distinct from that of growth hormone-releasing hormone.”

   DOI ↗PubMed ↗

Straight answers

Questions, answered