Bombesin receptors

Overview

Mammalian bombesin (Bn) receptors comprise 3 subtypes: BB₁, BB₂, BB₃. BB₁ and BB₂ are activated by the endogenous ligands neuromedin B (NMB), gastrin-releasing peptide (GRP), and GRP-(18-27). bombesin is... [read more] a tetra-decapeptide, originally derived from amphibians. The three Bn receptor subtypes couple primarily to the G_q/11 and G_12/13 family of G proteins [1]. Each of these receptors is widely distributed in the CNS and peripheral tissues [1,2,3,4,5,6]. Activation of BB₁ and BB₂ receptors causes a wide range of physiological/pathophysiogical actions, including the stimulation of normal and neoplastic tissue growth, smooth-muscle contraction, gastrointestinal motility, feeding behavior, secretion and many central nervous system effects including regulation of circadian rhythm, body temperature control, sighing and mediation of pruritus [1,3,7,8,9,10,11,12,13,14]. A physiological role for the BB₃ receptor has yet to be fully defined although recently studies suggest an important role in glucose and insulin regulation, metabolic homeostasis, feeding, regulation of body temperature, obesity, diabetes mellitus and growth of normal/neoplastic tissues [2,15,16,17,18,19]. Bn receptors are one of the most frequently overexpressed receptors in cancers and are receiving increased attention for their roles in tumor growth, as well as for tumour imaging and for receptor targeted cytotoxicity [8,20,21,22].

References

1. Jensen RT, Battey JF, Spindel ER, et al. International Union of Pharmacology. LXVIII. Mammalian bombesin receptors: nomenclature, distribution, pharmacology, signaling, and functions in normal and disease states. Pharmacol Rev 2008;60:1-42.
2. González N, Moreno P, Jensen RT. Bombesin receptor subtype 3 as a potential target for obesity and diabetes. Expert Opin Ther Targets 2015;19:1153-70.
3. Ramos-Álvarez I, Moreno P, Mantey SA, et al. Insights into bombesin receptors and ligands: Highlighting recent advances. Peptides 2015;72:128-44.
4. Sano H, Feighner SD, Hreniuk DL, et al. Characterization of the bombesin-like peptide receptor family in primates. Genomics 2004;84:139-46.
5. Porcher C, Juhem A, Peinnequin A, et al. Bombesin receptor subtype-3 is expressed by the enteric nervous system and by interstitial cells of Cajal in the rat gastrointestinal tract. Cell Tissue Res 2005;320:21-31.
6. Zhang L, Parks GS, Wang Z, et al. Anatomical characterization of bombesin receptor subtype-3 mRNA expression in the rodent central nervous system. J Comp Neurol 2013;521:1020-39.
7. Li P, Janczewski WA, Yackle K, et al. The peptidergic control circuit for sighing. Nature 2016;530:293-297.
8. Moreno P, Ramos-Álvarez I, Moody TW, et al. Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment. Expert Opin Ther Targets 2016;20:1055-73.
9. Qu X, Wang H, Liu R. Recent insights into biological functions of mammalian bombesin-like peptides and their receptors. Curr Opin Endocrinol Diabetes Obes 2018;25:36-41.
10. Moody TW, Merali Z. Bombesin-like peptides and associated receptors within the brain: distribution and behavioral implications. Peptides 2004;25:511-520.
11. Sun YG, Chen ZF. A gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord. Nature 2007;448:700-3.
12. Gajjar S, Patel BM. Neuromedin: An insight into its types, receptors and therapeutic opportunities. Pharmacol Rep 2017;69:438-447.
13. Chen XJ, Sun YG. Central circuit mechanisms of itch. Nat Commun 2020;11:3052.
14. Wan L, Jin H, Liu XY, et al. Distinct roles of NMB and GRP in itch transmission. Sci Rep 2017;7:15466.
15. Li M, Liang P, Liu D, et al. Bombesin Receptor Subtype-3 in Human Diseases. Arch Med Res 2019;50:463-467.
16. Majumdar ID, Weber HC. Biology and pharmacology of bombesin receptor subtype-3. Curr Opin Endocrinol Diabetes Obes 2012;19:3-7.
17. Ohki-Hamazaki H, Watase K, Yamamoto K, et al. Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity. Nature 1997;390:165-9.
18. Xiao C, Reitman ML. Bombesin-Like Receptor 3: Physiology of a Functional Orphan. Trends Endocrinol Metab 2016;27:603-5.
19. Moreno P, Mantey SA, Lee SH, et al. A possible new target in lung-cancer cells: The orphan receptor, bombesin receptor subtype-3. Peptides 2018;101:213-226.
20. Sancho V, Di Florio A, Moody TW, et al. Bombesin receptor-mediated imaging and cytotoxicity: review and current status. Curr Drug Deliv 2011;8:79-134.
21. Baratto L, Duan H, Mäcke H, et al. Imaging the Distribution of Gastrin-Releasing Peptide Receptors in Cancer. J Nucl Med 2020;61:792-798.
22. Maina T, Nock BA. From Bench to Bed: New Gastrin-Releasing Peptide Receptor-Directed Radioligands and Their Use in Prostate Cancer. PET Clin 2017;12:205-217.

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