GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Growth hormone secretagogues protect mouse cardiomyocytes from in vitro ischemia/reperfusion injury through regulation of intracellular calcium.
Ma. Yi Y; Zhang. Lin L; Edwards. Joshua N JN; Launikonis. Bradley S BS; Chen. Chen C
Key Findings
- Ghrelin (10 nM) and hexarelin (1 nM) given before or after ischemia prevented loss of heart‑cell contractility and calcium signaling in mouse cardiomyocytes.
- The protective effect depended on activation of the GHS‑R1a receptor and restoration of phosphorylated phospholamban, which maintains sarcoplasmic‑reticulum calcium stores.
- A GHS‑R1a antagonist ([D‑Lys3]‑GHRP‑6) completely blocked the benefits, confirming the receptor‑mediated mechanism.
Practical Outcomes
- For biohackers, the study suggests that activating GHS‑R1a (e.g., with ghrelin or hexarelin) could theoretically protect heart muscle during brief oxygen loss, but the work is limited to mouse cells and uses compounds not widely available. It does not provide dosing guidance for GHRP‑6 itself, and the antagonist used is a modified form, so there’s no direct protocol to apply. The main takeaway is that GHS‑R1a activation may be cardioprotective, but more human data are needed before any real‑world use.
Summary
In mouse heart cells, the natural hormone ghrelin and the synthetic peptide hexarelin helped keep the cells beating normally after a simulated heart attack by preserving calcium handling inside the cells. They did this by activating the GHS‑R1a receptor and keeping a protein called phospholamban (p‑PLB) phosphorylated, which protects the calcium stores needed for contraction. When a GHS‑R1a blocker (a modified version of GHRP‑6) was added, the protective effects disappeared, showing the importance of that receptor pathway.
Abstract
Ischemic heart disease is a leading cause of mortality. To study this disease, ischemia/reperfusion (I/R) models are widely used to mimic the process of transient blockage and subsequent recovery of cardiac coronary blood supply. We aimed to determine whether the presence of the growth hormone secretagogues, ghrelin and hexarelin, would protect/improve the function of heart from I/R injury and to examine the underlying mechanisms. Isolated hearts from adult male mice underwent 20 min global ischemia and 30 min reperfusion using a Langendorff apparatus. Ghrelin (10 nM) or hexarelin (1 nM) was introduced into the perfusion system either 10 min before or after ischemia, termed pre- and post-treatments. In freshly isolated cardiomyocytes from these hearts, single cell shortening, intracellular calcium ([Ca(2+)](i)) transients and caffeine-releasable sarcoplasmic reticulum (SR) Ca(2+) were measured. In addition, RT-PCR and Western blots were used to examine the expression level of GHS receptor type 1a (GHS-R1a), and phosphorylated phospholamban (p-PLB), respectively. Ghrelin and hexarelin pre- or post-treatments prevented the significant reduction in the cell shortening, [Ca(2+)](i) transient amplitude and caffeine-releasable SR Ca(2+) content after I/R through recovery of p-PLB. GHS-R1a antagonists, [D-Lys3]-GHRP-6 (200 nM) and BIM28163 (100 nM), completely blocked the effects of GHS on both cell shortening and [Ca(2+)](i) transients. Through activation of GHS-R1a, ghrelin and hexarelin produced a positive inotropic effect on ischemic cardiomyocytes and protected them from I/R injury probably by protecting or recovering p-PLB (and therefore SR Ca(2+) content) to allow the maintenance or recovery of normal cardiac contractility. These observations provide supporting evidence for the potential therapeutic application of ghrelin and hexarelin in patients with cardiac I/R injury.
Study Information
pubmed
2012
2012-04-06T00:00:00.000Z
10.1371/journal.pone.0035265
36
39