Hexarelin

Hexarelin, also called examorelin, is a synthetic hexapeptide with the sequence His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2, molecular weight near 887 g/mol and CAS 140703-51-1. It differs from GHRP-6 by a single methyl group on the second-position D-tryptophan. Like the other peptides of that series it acts at the G protein-coupled growth hormone secretagogue receptor of pituitary and hypothalamus, whose endogenous ligand is the octanoylated stomach peptide ghrelin; hexarelin is unusual in the series for also binding a second, non-GHS-R target.

Hexarelin in the research literature

Photoaffinity labelling of rat cardiac membranes with a radioactive derivative of hexarelin identified an 84 kDa binding protein whose N-terminal sequence matched rat CD36, a glycoprotein expressed in cardiomyocytes and microvascular endothelial cells. In perfused hearts, hexarelin raised coronary perfusion pressure in a concentration-related manner, an effect absent in hearts from CD36-null mice and from CD36-deficient rats.

A later rodent cardiac study reported that changes in IL-1beta and IL-1Ra expression following hexarelin exposure were reversed by the GHS-R antagonist D-Lys3-GHRP-6, which the authors took as evidence for a contribution of cardiac GHS-R1a receptors alongside CD36. Hexarelin has also been used as a comparator against equimolar ghrelin in the same model system.