Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Gastrin-Releasing Peptide Receptor (GRPR)

  • Alessia Parascandolo
  • Maria Domenica CastelloneEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101646


Historical Background

The human gastrin-releasing peptide receptor (hGRPR) gene was cloned in 1990 from NIH3T3 cells and located on chromosome X (Xp22.2–Xp22.13). It encodes a seven-transmembrane α-helices G protein-coupled receptor (GPCR) of 384-aa, interacting with large heterotrimeric G proteins of the Gαq and Gα12/ Gα13 families. The main GRPR ligands are represented by bombesin-like peptides (BLPs), including gastrin-releasing peptide (GRP) that is a peptide originally isolated from porcine stomach, synthesized as a precursor of 148-aa (PreproGRP) and post-translationally modified as a mature 27-aa neuropeptide. GRP is the mammalian homolog of the amphibian 14-aa peptide bombesin (BBS), sharing the same C-terminal sequence and binding to the same receptor. Four BLP binding receptor subtypes have been isolated: receptor subtype 1, termed GRPR, which binds BBS and GRP with high affinity; receptor subtype 2 binding neuromedin...

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  1. Bolton P, Powell J, Rutter M, Buckle V, Yates JR, Ishikawa-Brush Y, Monaco AP. Autism, mental retardation, multiple exostoses and short stature in a female with 46,X,t(X;8)(p22.13;q22.1). Psychiatr Genet. 1995;5:51–5.PubMedCrossRefGoogle Scholar
  2. Castellone MD, Laukkanen MO, Teramoto H, Bellelli R, Alì G, Fontanini G, Santoro M, Gutkind JS. Cross talk between the bombesin neuropeptide receptor and Sonic hedgehog pathways in small cell lung carcinoma. Oncogene. 2015 Mar 26;34(13):1679–87.PubMedCrossRefGoogle Scholar
  3. Dal-Pizzol F, Di Leone LP, Ritter C, Martins MR, Reinke A, Pens Gelain D, Zanotto-Filho A, de Souza LF, Andrades M, Barbeiro DF, Bernard EA, Cammarota M, Bevilaqua LR, Soriano FG, Cláudio J, Moreira F, Roesler R, Schwartsmann G. Gastrin-releasing peptide receptor antagonist effects on an animal model of sepsis. Am J Respir Crit Care Med. 2006;173:84–90.PubMedCrossRefGoogle Scholar
  4. Furness JB, Kunze WA, Clerc N. The intestine as a sensory organ: neural, endocrine, and immune responses. Am J Phys. 1999;277:922–8.Google Scholar
  5. Ghatei MA, Jung RT, Stevenson JC, Hillyard CJ, Adrian TE, Lee YC, Christofides ND, Sarson DL, Mashiter K, MacIntyre I, Bloom SR. Bombesin: action on gut hormones and calcium in man. J Clin Endocrinol Metab. 1982;54:980–5.PubMedCrossRefGoogle Scholar
  6. Gupta RA, Dubois RN. Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer. 2001;1:11–21.PubMedCrossRefGoogle Scholar
  7. Helmich MR, Ives KL, Udupi V, et al. Multiple protein kinase pathways are involved in gastrin-releasing peptide receptor-regulated secretion. J Biol Chem. 1999;274:23901–9.CrossRefGoogle Scholar
  8. Jensen RT, Coy DH, Saeed ZA, Heinz-Erian P, Mantey S, Gardner JD. Interaction of bombesin and related peptides with receptors on pancreatic acinar cells. Ann N Y Acad Sci. 1988;547:138–49.PubMedCrossRefGoogle Scholar
  9. Jensen JA, Carroll RE, Benya RV. The case for gastrin-releasing peptide acting as a morphogen when it and its receptor are aberrantly expressed in cancer. Peptides. 2001;22:689–99.PubMedCrossRefGoogle Scholar
  10. Kurose H. Gα12 and Gα13 as key regulatory mediator in signal transduction. Life Sci. 2003;74:155–61.PubMedCrossRefGoogle Scholar
  11. Laukkanen MO, Castellone MD. Gastrin-releasing peptide receptor targeting in cancer treatment: Emerging signaling networks and therapeutic applications. Curr Drug Targets. 2016;17:508–14.PubMedCrossRefGoogle Scholar
  12. Poitras P, Trudel L, Miller P, Gu CM. Regulation of motilin release: studies with ex vivo perfused canine jejunum. Am J Phys. 1997;272:G4–9.Google Scholar
  13. Rao PN, Klinepeter K, Stewart W, Hayworth R, Grubs R, Pettenati MJ. Molecular cytogenetic analysis of a duplication Xp in a male: further delineation of a possible sex influencing region on the X chromosome. Hum Genet. 1994;94:149–53.PubMedCrossRefGoogle Scholar
  14. Roesler R, Luft T, Oliveira SH, et al. Molecular mechanisms mediating gastrin-releasing peptide receptor modulation of memory consolidation in the hippocampus. Neuropharmacology. 2006;51:350–7.PubMedCrossRefGoogle Scholar
  15. Roesler R, Schwartsmann G. Gastrin-releasing peptide receptors in the central nervous system: role in brain function and as a drug target. Front Endocrinol. 2012;3(159).Google Scholar
  16. Severi C, Jensen RT, Erspamer V, D’Arpino L, Coy DH, Torsoli A, Delle Fave G. Different receptors mediate the action of bombesin-related peptides on gastric smooth muscle cells. Am J Phys. 1991;260:G683–90.Google Scholar
  17. Siehler S. Regulation of RhoGEF proteins by G12/13-coupled receptors. Br J Pharmacol. 2009;158:41–9.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Watkins DN, Berman DM, Baylin SB. Hedgehog signaling: progenitor phenotype in small-cell lung cancer. Cell Cycle. 2003;2:196–8.PubMedCrossRefGoogle Scholar
  19. Weigert N, Li YY, Lippl F, Coy DH, Classen M, Schusdziarra V. Role of endogenous bombesin-peptides during vagal stimulation of gastric acid secretion in the rat. Neuropeptides. 1996;30:521–7.PubMedCrossRefGoogle Scholar
  20. Zheng R, Iwase A, Shen R, Goodman Jr OB, Sugimoto N, Takuwa Y, Lerner DJ, Nanus DM. Neuropeptide-stimulated cell migration in prostate cancer cells is mediated by RhoA kinase signaling and inhibited by neutral endopeptidase. Oncogene. 2006;25:5942–52.PubMedCrossRefGoogle Scholar

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© Springer International Publishing AG 2018

Authors and Affiliations

  • Alessia Parascandolo
    • 1
  • Maria Domenica Castellone
    • 2
    Email author
  1. 1.IRCCS SDNNaplesItaly
  2. 2.Institute of Experimental Endocrinology and Oncology (IEOS)CNRNaplesItaly