Appetite-Modifying Effects of Bombesin Receptor Subtype-3 Agonists
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.
KeywordsBombesin receptor subtype-3 Bombesin-like peptides Energy homeostasis Gastrin-releasing peptide Mammalian bombesin receptors Neuromedin B Obesity Synthetic BRS-3 agonist
- Kuiper P, Verspaget HW, Biemond I, de Jonge-Muller ES, van Eeden S, van Velthuysen ML, Taal BG, Lamers CB (2010) Expression and ligand binding of bombesin receptors in pulmonary and intestinal carcinoids The role of bombesin in carcinoids. J Endocrinol Invest. 2010 Nov 8. [Epub ahead of print] PubMed PMID: 21060250. PubMed accessed on November 13, 2011Google Scholar
- Sakamoto H, Matsuda K, Zuloaga DG, et al (2008) Sexually dimorphic gastrin releasing peptide system in the spinal cord controls male reproductive functions. Nat Neurosci 11:634–636Google Scholar
- Sakamoto H, Kawata M (2009) Gastrin-releasing peptide system in the spinal cord controls male sexual behaviour. J Neuroendocrinol 21:432–435Google Scholar
- Sakamoto H, Takanami K, Zuloaga DG, et al (2009) Androgen regulates the sexually dimorphic gastrin-releasing peptide system in the lumbar spinal cord that mediates male sexual function. Endocrinology 150:3672–3679Google Scholar