GPR8

GPR8 (also known as NPBWR2) is a class A G protein-coupled receptor that functions as a receptor for the endogenous neuropeptides B (NPB) and W (NPW), and is predominantly expressed in the central nervous system, particularly in discrete brain regions involved in neuroendocrine regulation and behavioral control^[1][2]. Mechanistically, GPR8 participates in neuropeptide-mediated signaling pathways that regulate feeding behavior, energy homeostasis, stress responses, and neuroendocrine function through ligand-dependent receptor activation^[2]. Activation of GPR8 by NPB or NPW triggers intracellular signaling involving adenylate cyclase- and phospholipase C-dependent pathways, indicating a role in hormone-regulated cellular responses^[3]. In human adrenocortical cells, GPR8 and its endogenous ligands enhance cortisol secretion, providing a physiologically relevant model linking neuropeptide signaling to endocrine regulation^[3]. Disease-related studies further associate the NPB/NPW-GPR8 signaling system with metabolic regulation, stress adaptation, emotion-related behaviors, and neuroendocrine homeostasis, supporting its utility in experimental investigations of central nervous system and endocrine functions^[2]. Compared with the closely related receptor GPR7 (NPBWR1), GPR8 shares substantial sequence homology and ligand recognition properties but represents a distinct receptor subtype with its own expression profile and signaling characteristics, making receptor-specific analyses important for mechanistic studies of the NPB/NPW system^[1][2]. For experimental applications, endogenous peptide agonists NPB and NPW remain the principal pharmacological tools used to investigate GPR8-dependent signaling and physiological functions^[2].