GRPR

GRPR, or gastrin-releasing peptide receptor, is a member of the bombesin receptor family and a G protein-coupled receptor. It binds gastrin-releasing peptide and related bombesin-like peptides, with affinity variations among ligands. The receptor is expressed in a range of tissues, including the central nervous system and peripheral organs, where it mediates various physiological responses triggered by GRP and its relatives.

In the central nervous system, GRPR participates in regulation of appetite and energy balance. In hypothalamic circuits, it influences feeding and satiety signaling. In peripheral tissues, GRPR modulates gastric acid secretion, pancreatic exocrine function, and smooth muscle activity. A notable finding from research is the identification of GRPR-expressing spinal neurons as mediators of itch sensation in mice, highlighting a role in somatosensory processing.

Mechanistically, GRPR is a seven-transmembrane receptor that primarily couples to Gq/11 proteins. Activation leads to phospholipase Cβ stimulation, generation of IP3 and DAG, an intracellular calcium rise, and downstream signaling including protein kinase C and mitogen-activated protein kinases. Receptor desensitization and internalization via β-arrestins modulate signaling duration.

Clinical relevance: GRPR is expressed in several cancers, notably prostate and breast cancers, and to a lesser extent in others. This has driven the development of GRPR-targeted imaging agents, such as radiolabeled bombesin/GRPR ligands for positron emission tomography, and research into receptor-targeted therapies. Ongoing work seeks to exploit GRPR expression for diagnosis and treatment, as well as to understand its role in cancer biology and pruritus.

Gene and family: The receptor is encoded by the GRPR gene and belongs to the bombesin receptor subfamily of G protein-coupled receptors.