Purpose of review: This review summarizes the results of recent studies regarding the biology and pharmacology of novel synthetic agonists and antagonists of the bombesin receptor subtype-3 (BRS-3).
Recent findings: All three mammalian bombesin receptors including gastrin-releasing peptide receptor, the neuromedin B receptor, and the BRS-3 have been shown to regulate energy balance and appetite and satiety. Studies indicate that the orphan BRS-3 is an important regulator of body weight, energy expenditure, and glucose homeostasis. Endogenous bombesin-like peptides bombesin, gastrin-releasing peptide, and neuromedin B receptor do not bind to BRS-3 and the endogenous BRS-3 ligand remains unknown. The novel synthesis of selective, high-affinity BRS-3 agonists and antagonists has recently been accomplished and showed that BRS-3 regulates energy balance independent of other established pathways and glucose-stimulated insulin secretion in the pancreatic islet cells. The availability of new BRS-3 selective agonists and antagonists will facilitate further elucidation of its role in energy homeostasis, and provides a potential approach for the pharmacological treatment of obesity and type 2 diabetes.
Summary: The native ligand of the G protein-coupled BRS-3 has not been identified as of now. However, novel synthesis of small-molecule, high-affinity agonists and antagonists on the BRS-3 was used in the recent studies and demonstrated an important role of BRS-3 in the regulation of energy homeostasis and glucose metabolism.