Mammalian bombesin (Bn) receptors comprise 3 subtypes: BB₁, BB₂, BB₃ (nomenclature recommended by the NC-IUPHAR Subcommittee on bombesin receptors, [7]). BB₁ and BB₂ are activated by the endogenous ligands gastrin-releasing peptide (GRP, P07492) (GRP), neuromedin B (NMB, P08949) (NMB) and GRP-(18-27) (GRP, P07492) (previously named neuromedin C). Bombesin is a tetradecapeptide, originally derived from amphibians. The three Bn receptor subtypes couple primarily to the G_q/11 and G_12/13 family of G proteins [7] (but see also [10,32]). Each of these receptors is widely distributed in the CNS and peripheral tissues [4,7,26-27,27,29,29,35]. Activation of BB₁ and BB₂ receptors causes a wide range of physiological actions, including the stimulation of normal and neoplastic tissue growth, smooth-muscle contraction, appetite and feeding behavior, secretion and many central nervous system effects [7-9,14,22,27,27]. A physiological role for the BB₃ receptor has yet to be fully defined although recently studies using receptor knockout mice and newly described agonists/antagonists suggest an important role in glucose and insulin regulation, metabolic homeostasis, feeding, regulation of body temperature and other CNS behaviors, obesity, diabetes mellitus and growth of normal/neoplastic tissues [4,15,15,25,25,34].

All three human subtypes may be activated by [D-Phe⁶,β-Ala¹¹,Phe¹³,Nle¹⁴]bombesin-(6-14) [18]. [D-Tyr⁶,Apa-4Cl¹¹,Phe¹³,Nle¹⁴]bombesin-(6-14) has more than 200-fold selectivity for BB₃ receptors over BB₁ and BB₂ [17-18,27-28].

* Key recommended reading is highlighted with an asterisk

Akiyama T, Tominaga M, Takamori K, Carstens MI, Carstens E. (2014) Role of spinal bombesin-responsive neurons in nonhistaminergic itch. J. Neurophysiol., 112 (9): 2283-9. [PMID:25122701]

Bédard T, Mountney C, Kent P, Anisman H, Merali Z. (2007) Role of gastrin-releasing peptide and neuromedin B in anxiety and fear-related behavior. Behav Brain Res, 179: 133-140. [PMID:17335915]

Carrieri A, Lacivita E, Belviso BD, Caliandro R, Mastrorilli P, Gallo V, Niso M, Leopoldo M. (2017) Structural Determinants in the Binding of BB2 Receptor Ligands: In Silico, X-Ray and NMR Studies in PD176252 Analogues. Curr Top Med Chem, 17 (14): 1599-1610. [PMID:27823569]

Dalm SU, Schrijver WA, Sieuwerts AM, Look MP, Ziel-van der Made AC, de Weerd V, Martens JW, van Diest PJ, de Jong M, van Deurzen CH. (2017) Prospects of Targeting the Gastrin Releasing Peptide Receptor and Somatostatin Receptor 2 for Nuclear Imaging and Therapy in Metastatic Breast Cancer. PLoS ONE, 12 (1): e0170536. [PMID:28107508]

* Ferreira CA, Fuscaldi LL, Townsend DM, Rubello D, Barros AL. (2017) Radiolabeled bombesin derivatives for preclinical oncological imaging. Biomed. Pharmacother., 87: 58-72. [PMID:28040598]

* González N, Moreno P, Jensen RT. (2015) Bombesin receptor subtype 3 as a potential target for obesity and diabetes. Expert Opin. Ther. Targets, 19 (9): 1153-70. [PMID:26066663]

Guo M, Qu X, Qin XQ. (2015) Bombesin-like peptides and their receptors: recent findings in pharmacology and physiology. Curr Opin Endocrinol Diabetes Obes, 22 (1): 3-8. [PMID:25517020]

* Jensen RT, Battey JF, Spindel ER, Benya RV. (2008) International Union of Pharmacology. LXVIII. Mammalian bombesin receptors: nomenclature, distribution, pharmacology, signaling, and functions in normal and disease states. Pharmacol. Rev., 60 (1): 1-42. [PMID:18055507]

* Jensen RT, Moody TW. (2013) Bombesin Peptides (Cancer). In Handbook of Biologically Active Peptides. 2nd Revised edition. Edited by Kastin AJ (Elsevier) 506-511. [ISBN:9780123850959]

Jensen RT, Moody TW. (2013) Bombesin-Related Peptides. In Handbook of Biologically Active Peptides. 2nd Revised edition. Edited by Kastin AJ (Elsevier) 1188-1196. [ISBN:9780123850959]

Ladenheim EE. (2013) Bombesin. In Handbook of Biologically Active Peptides. 2nd Revised edition. Edited by Kastin AJ (Elsevier) 1064-1070. [ISBN:9780123850959]

Liu XY, Wan L, Huo FQ, Barry DM, Li H, Zhao ZQ, Chen ZF. (2014) B-type natriuretic peptide is neither itch-specific nor functions upstream of the GRP-GRPR signaling pathway. Mol Pain, 10: 4. [PMID:24438367]

* Ramos-Álvarez I, Moreno P, Mantey SA, Nakamura T, Nuche-Berenguer B, Moody TW, Coy DH, Jensen RT. (2015) Insights into bombesin receptors and ligands: Highlighting recent advances. Peptides, 72: 128-44. [PMID:25976083]

Richter S, Wuest M, Krieger SS, Rogers BE, Friebe M, Bergmann R, Wuest F. (2013) Synthesis and radiopharmacological evaluation of a high-affinity and metabolically stabilized 18F-labeled bombesin analogue for molecular imaging of gastrin-releasing peptide receptor-expressing prostate cancer. Nucl. Med. Biol., 40 (8): 1025-34. [PMID:23969085]

Rick FG, Abi-Chaker A, Szalontay L, Perez R, Jaszberenyi M, Jayakumar AR, Shamaladevi N, Szepeshazi K, Vidaurre I, Halmos G et al.. (2013) Shrinkage of experimental benign prostatic hyperplasia and reduction of prostatic cell volume by a gastrin-releasing peptide antagonist. Proc. Natl. Acad. Sci. U.S.A., 110 (7): 2617-22. [PMID:23359692]

Rick FG, Buchholz S, Schally AV, Szalontay L, Krishan A, Datz C, Stadlmayr A, Aigner E, Perez R, Seitz S et al.. (2012) Combination of gastrin-releasing peptide antagonist with cytotoxic agents produces synergistic inhibition of growth of human experimental colon cancers. Cell Cycle, 11 (13): 2518-25. [PMID:22751419]

Roesler R, Schwartsmann G. (2012) Gastrin-releasing peptide receptors in the central nervous system: role in brain function and as a drug target. Front Endocrinol (Lausanne), 3: 159. [PMID:23251133]

* Sayegh AI. (2013) The role of bombesin and bombesin-related peptides in the short-term control of food intake. Prog Mol Biol Transl Sci, 114: 343-70. [PMID:23317790]

Shafik NF, Rahoma M, Elshimy RA, M Abou El kasem F. (2016) Prognostic Value of Prepro-Gastrin Releasing Peptide in Lung Cancer Patients; NCI-Prospective Study. Asian Pac. J. Cancer Prev., 17 (12): 6079-6083. [PMID:28124884]

Stoykow C, Erbes T, Maecke HR, Bulla S, Bartholomä M, Mayer S, Drendel V, Bronsert P, Werner M, Gitsch G et al.. (2016) Gastrin-releasing Peptide Receptor Imaging in Breast Cancer Using the Receptor Antagonist (68)Ga-RM2 And PET. Theranostics, 6 (10): 1641-50. [PMID:27446498]

Weber HC. (2015) Gastrointestinal peptides and itch sensation. Curr Opin Endocrinol Diabetes Obes, 22 (1): 29-33. [PMID:25485517]

Zhang J, Li D, Lang L, Zhu Z, Wang L, Wu P, Niu G, Li F, Chen X. (2016) 68Ga-NOTA-Aca-BBN(7-14) PET/CT in Healthy Volunteers and Glioma Patients. J. Nucl. Med., 57 (1): 9-14. [PMID:26449838]

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Subcommittee members: Robert T. Jensen (Chairperson) National Institute of Diabetes & Kidney Diseases National Institutes of Health Building 10 Room 9C-103 NIH Bethesda MD 20892 USA Jim Battey National Institute on Deafness and Other Communication Disorders Building 31 Room 3C02 NIH Bethesda MD 20892 USA Richard V. Benya University of Illinois Section of Digestive Diseases and Nutrition 840 South Wood Street (M/C 716) Chicago Illinois 60612 USA Terry W. Moody National Institutes of Health Center for Cancer Research Bethesda MD USA