GHRP-6

Scientific Description

GHRP-6 is a synthetic hexapeptide and prototypical growth hormone secretagogue that acts primarily via the growth hormone secretagogue receptor type 1a (GHSR-1a), the canonical ghrelin receptor. It promotes pulsatile GH release from the anterior pituitary and has been exploited as a tool compound for dissecting ghrelin/GHSR-dependent pathways in multiple organ systems.

Research indicates that GHRP-6 is orally and sublingually active in rodents and exhibits moderate-to-high selectivity for its target receptor.

Structural Information

• Chemical Nature: Hexapeptide amide
• Sequence: His–D-Trp–Ala–Trp–D-Phe–Lys–NH₂

Major Experimental Domains

1. Cognitive Function and Synaptic Plasticity

Multiple rodent studies have characterized ghrelin/GHRP-6 signaling as a modulator of learning and memory:

• Food deprivation–induced ghrelin signaling enhances fear extinction and alters synaptic plasticity (LTD) in the lateral amygdala [1].
• Pharmacological blockade of GHSR-1a impairs memory encoding [2].
• Intra-amygdaloid ghrelin modulates spatial learning [3].

GHRP-6 is frequently utilized as a GH secretagogue model to probe how ghrelinergic pathways support memory consolidation and hippocampal function.

2. Ischemic Neuroprotection

In rodent models of cerebral ischemia and in coadministration paradigms with nIGF-1, GHRP-6 has been reported to [4][5]:

• Reduce apoptosis and excitotoxic cell death
• Attenuate neuroinflammatory responses
• Preserve cognitive performance when administered within a defined post-ischemic time window

These data support a neuroprotective role for ghrelin agonism in acute ischemic brain injury.

3. Dopaminergic Neuron Survival and Parkinsonian Phenotypes

Down-regulation of GHSR-1a on substantia nigra dopaminergic neurons has been linked to Parkinsonian motor dysfunction in rodent models [6]. Ghrelin agonists, including GHRP-6, are under investigation for their ability to:

• Limit apoptosis of nigrostriatal dopaminergic neurons
• Modify Parkinson’s disease-like phenotypes in preclinical systems

GHRP-6 thus serves as a useful probe for GHSR-mediated neuroprotection in basal ganglia circuitry.

4. Cutaneous Wound Healing and Scar Modulation

GHRP-6 has been evaluated in a range of cutaneous injury models, including burns and surgical wounds:

• Enhances survival of multiple cell types by reducing programmed cell death
• Accelerates angiogenesis and re-epithelialization, improving wound closure kinetics [7]
• Promotes organized extracellular matrix (ECM) and collagen deposition with superior mechanical properties of the healed tissue [7][8]
• Reduces development of hypertrophic and keloid-like scarring in experimental conditions [8]

These properties position GHRP-6 as a valuable experimental tool in dermal regeneration and fibrosis research.

5. Myocardial Ischemia–Reperfusion Injury

In porcine acute myocardial infarction models, post-ischemic GHRP-6 administration has been shown to [9]:

• Attenuate oxidant-induced cytotoxicity
• Decrease the extent of myocardial necrosis

This suggests a potential GHSR-mediated cardioprotective mechanism that preserves jeopardized but still viable myocardium in ischemia–reperfusion settings.

6. Motivational and Affective Neuroscience

Central GHSR-1a activation is increasingly recognized as a key modulator of reward and motivation:

• Region-specific ghrelin receptor stimulation modulates sex motivation in male rats [10].
• Ghrelin/GHSR signaling supports hippocampal neurogenesis and exerts antidepressant-like effects in chronic stress paradigms [11].

GHRP-6 and related analogues are therefore being utilized to interrogate the intersection of metabolic signaling, motivation, and mood regulation.

Safety Profile and Limitations

In preclinical models, GHRP-6 has displayed:

• Minimal to moderate adverse effects at experimentally relevant doses
• Low oral but excellent subcutaneous bioavailability in mice

Critical Limitation:
All efficacy, pharmacokinetic, and safety data summarized here are derived from non-human studies (in vivo and in vitro). No dosing or effect data should be extrapolated to humans.

Regulatory and Use Disclaimer

GHRP-6 supplied by Peptide Sciences is:

• For laboratory research and development use only
• Not for human consumption or clinical application
• Not for diagnostic, therapeutic, or veterinary use

Purchase and use are restricted to professionally qualified, licensed researchers.

Author and Scientific Acknowledgment

This review has been compiled and structured by Dr. Logan, M.D., Case Western Reserve University School of Medicine, with a B.S. in Molecular Biology.

Professor Marta Korbonits is cited as a leading contributor to the scientific understanding of growth hormone–releasing peptides and ghrelin analogues [12]. Her work has:

• Defined key endocrine actions of GH-releasing peptides on hypothalamic–pituitary function
• Elucidated molecular mechanisms of pituitary tumorigenesis
• Identified mutations in the AIP tumor suppressor gene and explored glucocorticoid-related regulation of metabolism

She currently serves as Professor of Endocrinology and Metabolism at Queen Mary University of London and Deputy Head of the William Harvey Research Institute.

No Endorsement Implied:
Professor Korbonits has no known affiliation with Peptide Sciences and does not endorse the sale or use of this product. She is referenced solely to acknowledge her peer-reviewed contributions to the underlying science.