Glossary
Ghrelin Receptor (GHS-R1a)
GHS-R1a is the ghrelin receptor that GHRPs and MK-677 act on. Its high constitutive activity, the acylation requirement and how it desensitises over time.
GHS-R1a, the growth hormone secretagogue receptor subtype 1a, is the working receptor for ghrelin and the site of action of all GHRPs. It is a class A G protein-coupled receptor present on somatotrophs in the pituitary, in the arcuate nucleus of the hypothalamus and on vagal afferent fibres, and it signals predominantly via Gq, phospholipase C and intracellular calcium.
Two distinctive properties
The first is a remarkably high level of constitutive activity: about half of the receptor’s maximum signalling happens with no ligand bound at all. This opens inverse agonism as a separate pharmacological strategy and makes antagonist studies harder to interpret. The second is that the natural ligand is only active in acylated form: ghrelin needs an octanoyl group on Ser3, attached by ghrelin O-acyltransferase, and des-acyl ghrelin fails to activate GHS-R1a. A truncated splice variant, GHS-R1b, cannot bind ghrelin and seems to influence how the 1a form is trafficked.
Consequences for research
Desensitisation during continuous agonist exposure is the main practical limitation in secretagogue studies, and it explains why rankings of acute potency — hexarelin strongest, ipamorelin most selective — fail to forecast responses across longer study periods.
Related terms
growth hormone secretagogue · GHRH. See the ghrelin research family, Ipamorelin, and Hexarelin vs Ipamorelin.