Bombesin receptor family (BBR)

The Bombesin receptor family consists of three distinct G protein-coupled receptors: the neuromedin B receptor (NMBR or BB1), the gastrin-releasing peptide receptor (GRPR or BB2), and the bombesin receptor subtype 3 (BRS3 or BB3) [PMID: 23110598]. These receptors are widely expressed in the central nervous system and the gastrointestinal tract, where they regulate critical physiological processes such as smooth muscle contraction, exocrine and endocrine secretion, feeding behavior, and body temperature [PMID: 15131245]. In the context of human disease, the GRPR is notably overexpressed in several major cancers, including prostate, breast, and small cell lung cancer, making it a high-priority target for molecular imaging and targeted radionuclide therapy [PMID: 28461593]. Additionally, the BRS3 receptor has emerged as a potential therapeutic target for metabolic disorders like obesity and type 2 diabetes due to its role in regulating energy expenditure and glucose homeostasis [PMID: 21822281]. Current pharmacological strategies focus on developing stable peptide analogs and non-peptide ligands that can either inhibit tumor growth as antagonists or deliver cytotoxic payloads as radiopharmaceuticals. However, therapeutic development must address challenges such as the high density of these receptors in healthy pancreatic tissue and the potential for off-target effects in the gut and brain.

Other names

BB receptorsGastrin-releasing peptide receptor familyNeuromedin B receptor familyBombesin-like peptide receptors

The mechanism of action involves the binding of peptide agonists or non-peptide antagonists to the receptor's extracellular and transmembrane domains, which modulates intracellular signaling via G proteins (primarily Gq/11 and G12/13) and phospholipase C. In oncology, radiolabeled bombesin analogs act as vehicles for targeted radionuclide therapy or diagnostic imaging by binding specifically to overexpressed receptors on tumor cells [PMID: 23110598, PMID: 28461593].