GHSR1a

GHSR1a (growth hormone secretagogue receptor 1a) is the only molecularly identified receptor for ghrelin and functions as a class A G protein-coupled receptor that mediates key neuroendocrine and metabolic signaling processes^[1][2]. Mechanistically, GHSR1a exhibits unusually high constitutive activity, enabling intracellular signaling even in the absence of ligand binding, and this intrinsic property contributes to downstream G protein-dependent pathways that regulate physiological functions including growth hormone secretion and energy homeostasis^[3][4][5]. Constitutive signaling is supported by specific structural determinants within the receptor and can activate pathways involving PLC/IP₃/Ca²⁺ and CREB-related signaling networks^[6][3]. In disease and experimental contexts, altered GHSR1a activity has been associated with growth regulation, and loss of receptor constitutive activity has been linked to familial short stature, highlighting the physiological relevance of basal receptor signaling^[7][3]. GHSR1a is also broadly expressed in the central nervous system, where it participates in neural processes related to feeding behavior, obesity, addiction, inflammation, proliferation, and apoptosis^[8]. Compared with the related isoform GHSR1b, GHSR1a is the functional ghrelin-binding receptor, whereas GHSR1b is a truncated, non-signaling isoform that does not bind ghrelin but modulates GHSR1a trafficking, surface expression, constitutive activity, and receptor pharmacology through oligomerization or heterodimerization mechanisms^[9][10][6]. For experimental applications, both agonists and inverse agonists have been widely used to investigate receptor activation mechanisms and constitutive signaling, providing valuable tools for studying ghrelin receptor biology and ligand-directed pharmacology^[11][12].