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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
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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 Gq/11 and G12/13 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].
BB1 receptor
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BB2 receptor
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BB3 receptor
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* 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]
1. Benya RV, Kusui T, Pradhan TK, Battey JF, Jensen RT. (1995) Expression and characterization of cloned human bombesin receptors. Mol Pharmacol., 47: 10-20. [PMID:7838118]
2. Chobanian HR, Guo Y, Liu P, Chioda M, Lanza Jr TJ, Chang L, Kelly TM, Kan Y, Palyha O, Guan XM et al.. (2012) Discovery of MK-7725, A Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Obesity. ACS Med Chem Lett, 3 (3): 252-6. [PMID:24900461]
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4. 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]
5. Guan XM, Chen H, Dobbelaar PH, Dong Y, Fong TM, Gagen K, Gorski J, He S, Howard AD, Jian T et al. (2010) Regulation of energy homeostasis by bombesin receptor subtype-3: selective receptor agonists for the treatment of obesity. Cell Metabolism, 11 (2): 101-112. [PMID:20096642]
6. He S, Dobbelaar PH, Liu J, Jian T, Sebhat IK, Lin LS, Goodman A, Guo C, Guzzo PR, Hadden M et al.. (2010) Discovery of substituted biphenyl imidazoles as potent, bioavailable bombesin receptor subtype-3 agonists. Bioorg. Med. Chem. Lett., 20 (6): 1913-7. [PMID:20167483]
7. 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]
8. Jensen RT, Moody TW. (2013) Bombesin Peptides (Cancer). In Handbook of Biologically Active Peptides Edited by Kastin AJ (Elsevier) 506-11. [ISBN:9780123850959]
9. Jensen RT, Moody TW. (2013) Bombesin-Related Peptides. In Handbook of Biologically Active Peptides Edited by Kastin AJ (Elsevier) 118-96. [ISBN:9780123850959]
10. Jian X, Sainz E, Clark WA, Jensen RT, Battey JF, Northup JK. (1999) The bombesin receptor subtypes have distinct G protein specificities. J. Biol. Chem., 274 (17): 11573-81. [PMID:10206964]
11. Leban JJ, Kull FC Jr, Landavazo A, Stockstill B, McDermed JD. (1993) Development of potent gastrin-releasing peptide antagonists having aD-Pro-psi(CH2NH)-Phe-NH2 C terminus. Proc Natl Acad Sci U S A., 90: 1922-1926. [PMID:8446610]
12. Liu P, Lanza Jr TJ, Chioda M, Jones C, Chobanian HR, Guo Y, Chang L, Kelly TM, Kan Y, Palyha O et al.. (2011) Discovery of benzodiazepine sulfonamide-based bombesin receptor subtype 3 agonists and their unusual chirality. ACS Med Chem Lett, 2 (12): 933-7. [PMID:24900283]
13. Llinares M, Devin C, Chaloin O, Azay J, Noel-Artis AM, Bernad N, Fehrentz JA, Martinez J. (1999) Syntheses and biological activities of potent bombesin receptor antagonists. J Pept Res., 53: 275-283. [PMID:10231715]
14. Majumdar ID, Weber HC. (2011) Biology of mammalian bombesin-like peptides and their receptors. Curr Opin Endocrinol Diabetes Obes, 18 (1): 68-74. [PMID:21042212]
15. Majumdar ID, Weber HC. (2012) Biology and pharmacology of bombesin receptor subtype-3. Curr Opin Endocrinol Diabetes Obes, 19 (1): 3-7. [PMID:22157398]
16. Mantey S, Frucht H, Coy DH, Jensen RT. (1993) Characterization of bombesin receptors using a novel, potent, radiolabeled antagonist that distinguishes bombesin receptor subtypes. Mol Pharmacol., 43: 762-774. [PMID:7684815]
17. Mantey SA, Coy DH, Entsuah LK, Jensen RT. (2004) Development of Bombesin Analogues With Conformationally-Restricted Amino Acid Substitutions With Enhanced Selectivity for the Orphan Receptor, hBRS-3. J Pharmacol Exp Ther., 310: 1161-1170. [PMID:15102928]
18. Mantey SA, Weber HC, Sainz E, Akeson M, Ryan RR, Pradhan TK, Searles RP, Spindel ER, Battey JF, Coy DH, Jensen RT. (1997) Discovery of a high affinity radioligand for the human orphan receptor, bombesin receptor subtype 3, which demonstrates that it has a uniquepharmacology compared with other mammalian bombesin receptors. J Biol Chem., 272: 26062-26071. [PMID:9325344]
19. Matsufuji T, Shimada K, Kobayashi S, Ichikawa M, Kawamura A, Fujimoto T, Arita T, Hara T, Konishi M, Abe-Ohya R et al.. (2015) Synthesis and biological evaluation of novel chiral diazepine derivatives as bombesin receptor subtype-3 (BRS-3) agonists incorporating an antedrug approach. Bioorg. Med. Chem., 23 (1): 89-104. [PMID:25497965]
20. Matsufuji T, Shimada K, Kobayashi S, Kawamura A, Fujimoto T, Arita T, Hara T, Konishi M, Abe-Ohya R, Izumi M et al.. (2014) Discovery of novel chiral diazepines as bombesin receptor subtype-3 (BRS-3) agonists with low brain penetration. Bioorg. Med. Chem. Lett., 24 (3): 750-5. [PMID:24412111]
21. Moody TW, Mantey SA, Moreno P, Nakamura T, Lacivita E, Leopoldo M, Jensen RT. (2015) ML-18 is a non-peptide bombesin receptor subtype-3 antagonist which inhibits lung cancer growth. Peptides, 64: 55-61. [PMID:25554218]
22. Moody TW, Merali Z. (2004) Bombesin-like peptides and associated receptors within the brain: distribution and behavioral implications. Peptides, 25: 511-520. [PMID:15134870]
23. Moreno P, Mantey SA, Nuche-Berenguer B, Reitman ML, Gonzalez N, , Coy DH, Jensen RT. (2013) Comparative Pharmacology of Bombesin Receptor Subtype-3, Nonpeptide Agonist MK-5046, a Universal Peptide Agonist, and Peptide Antagonist Bantag-1 for Human Bombesin Receptors. Pharmacol Exp Therap, 347 (1): 100-116. [PMID:23892571]
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25. Ohki-Hamazaki H, Watase K, Yamamoto K, Ogura H, Yamano M, Yamada K, Maeno H, Imaki J, Kikuyama S, Wada E, Wada K. (1997) Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity. Nature., 390: 165-169. [PMID:9367152]
26. Porcher C, Juhem A, Peinnequin A, Bonaz B. (2005) 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, 320: 21-31. [PMID:15726424]
27. 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]
28. Ramos-Álvarez I, Nakamura T, Mantey SA, Moreno P, Nuche-Berenguer B, Jensen RT. (2016) Novel chiral-diazepines function as specific, selective receptor agonists with variable coupling and species variability in human, mouse and rat BRS-3 receptor cells. Peptides, 75: 8-17. [PMID:26524625]
29. Sano H, Feighner SD, Hreniuk DL, Iwaasa H, Sailer AW, Pan J, Reitman ML, Kanatani A, Howard AD, Tan CP. (2004) Characterization of the bombesin-like peptide receptor family in primates. Genomics, 84: 139-146. [PMID:15203211]
30. Sebhat IK, Franklin C, Lo MM, Chen D, Jewell JP, Miller R, Pang J, Palyha O, Kan Y, Kelly TM et al.. (2011) Discovery of MK-5046, a Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Obesity. ACS Med Chem Lett, 2 (1): 43-7. [PMID:24900253]
31. Tokita K, Katsuno T, Hocart SJ, Coy DH, Llinares M, Martinez J, Jensen RT. (2001) Molecular basis for selectivity of high affinity peptide antagonists for the gastrin-releasing peptide receptor. J Biol Chem., 276: 36652-36663. [PMID:11463790]
32. Uehara H, González N, Sancho V, Mantey SA, Nuche-Berenguer B, Pradhan T, Coy DH, Jensen RT. (2011) Pharmacology and selectivity of various natural and synthetic bombesin related peptide agonists for human and rat bombesin receptors differs. Peptides, 32 (8): 1685-99. [PMID:21729729]
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Subcommittee members:
Robert T. Jensen (Chairperson)
Jim Battey
Richard V. Benya
Terry W. Moody |
Database page citation:
Robert T. Jensen, Jim Battey, Richard V. Benya, Terry W. Moody. Bombesin receptors. Accessed on 21/02/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=9.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Christopoulos A, Davenport AP, Kelly E, Marrion NV, Peters JA, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2017) The Concise Guide to PHARMACOLOGY 2017/18: G protein-coupled receptors. Br J Pharmacol. 174 Suppl 1: S17-S129.
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].