Mammalian bombesin (Bn) receptors comprise 3 subtypes: BB₁, BB₂, BB₃ (nomenclature recommended by the NC-IUPHAR Subcommittee on bombesin receptors, [10]). 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). 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 [10]. Each of these receptors is widely distributed in the CNS and peripheral tissues [6,10,34,36,39,48]. 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, feeding behavior, secretion and many central nervous system effects including regulation of circadian rhythm and mediation of pruritus [2,4,10-14,18,27,36,41,46]. 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 [6,19,29,33,47].

All three human subtypes may be activated by [D-Phe⁶,β-Ala¹¹,Phe¹³,Nle¹⁴]bombesin-(6-14) [22]. Agonists [D-Tyr⁶,Apa-4Cl11,Phe¹³,Nle1⁴]bombesin-(6-14), MK-5046, and the oral diazepine, 9G have more than 200-, 300-, and 300-fold selectivity for human BB₃ receptors over BB₁ and BB₂ [21-22,36-37]. In nonplacental animals GRP and NMB activate BB₃ (BRS-3) including in chickens [25,42]- but not in placental animals where BRS-3 functions as an orphan receptor which is constitutively active [42]. All three human bombesin receptor subtypes are inhibited with low affinity by the nonpeptide antagonist AM-37 (K_i 1-5 μM) and its S-enantiomer, ST-36 (PubChem CID 122181320; K_i 7-10 μM) [28].

* Key recommended reading is highlighted with an asterisk

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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]

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* 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]

* Maina T, Nock BA, Kulkarni H, Singh A, Baum RP. (2017) Theranostic Prospects of Gastrin-Releasing Peptide Receptor-Radioantagonists in Oncology. PET Clin, 12 (3): 297-309. [PMID:28576168]

* Moreno P, Ramos-Álvarez I, Moody TW, Jensen RT. (2016) Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment. Expert Opin. Ther. Targets, 20 (9): 1055-73. [PMID:26981612]

* Qu X, Wang H, Liu R. (2018) Recent insights into biological functions of mammalian bombesin-like peptides and their receptors. Curr Opin Endocrinol Diabetes Obes, 25 (1): 36-41. [PMID:29120926]

* 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]

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]

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]

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