Studies on
bombesin-like
peptides (BLP) and their respective mammalian receptors (Bn-r) have demonstrated a significant
biological impact on a broad array of physiological and pathophysiological conditions. Pharmacological experiments in vitro and in vivo as well as utilization of genetic rodent models of the
gastrin-releasing peptide receptor (GRP-R/BB2-
receptor), neuromedin B receptor (NMB-R/BB1-receptor), and the
bombesin receptor subtype-3 (BRS-3/BB3-receptor) further delineated their role in health and disease. All three mammalian
bombesin receptors have been shown to possess some role in the regulation of energy balance and appetite and satiety. Compelling experimental evidence has accumulated indicating that the orphan
BRS-3 is an important regulator of
body weight, energy expenditure, and
glucose homeostasis.
BRS-3 possesses no high affinity to the endogenous
bombesin-like
peptides (BLP)
bombesin, GRP, and NMB, and its endogenous
ligand remains unknown. Recently, the synthesis of novel, selective high-affinity
BRS-3 agonists and antagonists has been accomplished and has demonstrated that
BRS-3 regulates energy balance independent of other established pathways. Accordingly, 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.