Hexarelin

Hexarelin is a synthetic hexapeptide (His-D-2MeTrp-Ala-Trp-D-Phe-Lys-NH2) belonging to the growth hormone secretagogue (GHS) class, acting as a potent agonist of the ghrelin receptor (GHS-R1a). Like other GHRPs, hexarelin activates Galphaq/PLCbeta/IP3/PKC signalling in pituitary somatotropes upon GHS-R1a binding, stimulating GH release through a pathway distinct from GHRH/cAMP signalling. Hexarelin is distinguished from other GHRPs by its additional activity at the CD36 receptor — a scavenger receptor expressed on cardiac myocytes and endothelial cells. Through CD36 receptor interaction, hexarelin exhibits cardioprotective signalling effects that are independent of its GH-releasing activity: studies have demonstrated that hexarelin protects cardiac tissue from ischaemia-reperfusion injury, reduces cardiomyocyte apoptosis, and modulates cardiac calcium handling. The CD36 receptor pathway also influences fatty acid metabolism in cardiac tissue, as CD36 is a major fatty acid transporter. This dual activity — potent GH release through GHS-R1a and cardioprotective signalling through CD36 — makes hexarelin a unique research tool for studying both the growth hormone secretagogue axis and cardiac signalling pathways, and for investigating the intersection of metabolic and cardiovascular signalling.