Ghrelin Receptor (GHS-R1a)

GHS-R1a is the growth hormone secretagogue receptor type 1a — the functional receptor for ghrelin and the target of every GHRP. It is a class A G protein-coupled receptor expressed on pituitary somatotrophs, in the hypothalamic arcuate nucleus, and in the vagal afferents, and it signals mainly through Gq to phospholipase C and intracellular calcium.

Two features worth knowing

First, the receptor has unusually high constitutive activity — roughly half its maximal signalling occurs without any ligand bound — which makes inverse agonism a distinct pharmacological option and complicates interpretation of antagonist experiments. Second, its endogenous ligand only works when acylated: ghrelin requires an octanoyl group on Ser3, installed by ghrelin O-acyltransferase, and des-acyl ghrelin does not activate GHS-R1a. A splice variant, GHS-R1b, is truncated, does not bind ghrelin, and appears to modulate trafficking of the 1a form.

Why it matters

Receptor desensitisation under sustained agonism is the practical constraint in secretagogue research and the reason acute potency rankings — hexarelin highest, ipamorelin most selective — do not predict responses over longer study periods.

Related terms

growth hormone secretagogue · GHRH. See the ghrelin research family, Ipamorelin, and Hexarelin vs Ipamorelin.