Gastrin-releasing peptide aka GRP and Pro-Gastrin-Releasing-Peptide aka Pro-GRP (and something called PreProGRP?)

Gastrin-releasing peptide, also known as GRP, is a neuropeptide, a regulatory molecule that has been implicated in a number of physiological and pathophysiological processes. Most notably, GRP stimulates the release of gastrin from the G cells of the stomach.

• The gene from which GRP is derived encodes a number of bombesin-like peptides.
  • ^{“Entrez Gene: GRP gastrin-releasing peptide”.}
  • ^{Spindel ER, Chin WW, Price J, Rees LH, Besser GM, Habener JF (September 1984). “Cloning and characterization of cDNAs encoding human gastrin-releasing peptide”. Proc. Natl. Acad. Sci. U.S.A. 81 (18): 5699–703. Bibcode:1984PNAS…81.5699S. doi:10.1073/pnas.81.18.5699. PMC 391778. PMID 6207529.}
  • ^{Spindel ER, Zilberberg MD, Habener JF, Chin WW (January 1986). “Two prohormones for gastrin-releasing peptide are encoded by two mRNAs differing by 19 nucleotides”. Proc. Natl. Acad. Sci. U.S.A. 83 (1): 19–23. Bibcode:1986PNAS…83…19S. doi:10.1073/pnas.83.1.19. PMC 322782. PMID 3001723.}
  • ^{Lebacq-Verheyden AM, Bertness V, Kirsch I, Hollis GF, McBride OW, Battey J (January 1987). “Human gastrin-releasing peptide gene maps to chromosome band 18q21”. Somat. Cell Mol. Genet. 13 (1): 81–6. doi:10.1007/BF02422302. PMID 3027901. S2CID 28347998.} 
• Its 148-amino acidpreproprotein, following cleavage of a signal peptide, is further processed to produce either the 27-amino acid gastrin-releasing peptide or the 10-amino acid neuromedin C.
  • ^{“Neuromedin C”. pubchem.ncbi.nlm.nih.gov.}

• These smaller peptides regulate numerous functions of the gastrointestinal and central nervous systems, including release of gastrointestinal hormones, smooth muscle cell contraction, and epithelial cell proliferation.
  • ^{“Entrez Gene: GRP gastrin-releasing peptide”.}

Function

• Gastrin-releasing peptide is a regulatory human peptide that elicits gastrin release and regulates gastric acid secretion and enteric motor function.
  • ^{Merali Z, McIntosh J, Anisman H (October 1999). “Role of bombesin-related peptides in the control of food intake”. Neuropeptides. 33 (5): 376–86. doi:10.1054/npep.1999.0054. PMID 10657515. S2CID 22270584} 
• The post-ganglionic fibers of the vagus nerve that innervate bombesin/GRP neurons of the stomach release GRP, which stimulates the G cells to release gastrin.

GRP is also involved in the biology of the circadian system, playing a role in the signaling of light to the master circadian oscillator in the suprachiasmatic nuclei of the hypothalamus.

Furthermore, GRP seems to mediate certain aspects of stress. This is the reason for the observed fact that atropine does not block the vagal effect on gastrin release.

Gene

• The human GRP gene is located on chromosome 18q21. PreproGRP (the unprocessed form of GRP) is encoded in three exons separated by two introns.
  • ^{Lebacq-Verheyden AM, Bertness V, Kirsch I, Hollis GF, McBride OW, Battey J (January 1987). “Human gastrin-releasing peptide gene maps to chromosome band 18q21”. Somat. Cell Mol. Genet. 13 (1): 81–6. doi:10.1007/BF02422302. PMID 3027901. S2CID 28347998.} 
• Alternative splicing results in multiple transcript variants encoding different isoforms.
  • ^{“Entrez Gene: GRP gastrin-releasing peptide”.}

Synthesis

• PreproGRP begins with signal peptidase cleavage to generate the proGRP, which is then processed by proteolytic cleavages, to form smaller GRP peptides.
  • ^{Merali Z, McIntosh J, Anisman H (October 1999). “Role of bombesin-related peptides in the control of food intake”. Neuropeptides. 33 (5): 376–86. doi:10.1054/npep.1999.0054. PMID 10657515. S2CID 22270584}

• These smaller peptides are released by the post-ganglionic fibers of the vagus nerve, which innervate the G cells of the stomach and stimulate them to release gastrin. GRP regulates numerous functions of the gastrointestinal and central nervous systems, including release of gastrointestinal hormones, smooth muscle cell contraction, and epithelial cell proliferation.
  • ^{Merali Z, McIntosh J, Anisman H (October 1999). “Role of bombesin-related peptides in the control of food intake”. Neuropeptides. 33 (5): 376–86. doi:10.1054/npep.1999.0054. PMID 10657515. S2CID 22270584}

Clinical significance

• Gastrin-releasing peptide and neuromedin C, it is postulated, play a role in human cancers of the lung, colon, stomach, pancreas, breast, and prostate.
  • “Entrez Gene: GRP gastrin-releasing peptide”.

Pro-Gastrin-Releasing-Peptide

• Pro-Gastrin-Releasing-Peptide, also known as Pro-GRP, is a Gastrin-Releasing-Peptide (GRP) precursor, a neurotransmitter that belongs to the bombesine/neuromedin B family. GRP stimulates the secretion of gastrin in order to increase the acidity of the gastric acid. Pro-GRP is a peptide composed of 125 amino acids, expressed in the nervous system and digestive tract.
  • ^{Dumesny, Chelsea; Patel, Oneel; Lachal, Shamilah; Giraud, Andrew S.; Baldwin, Graham S.; Shulkes, Arthur (2006). “Synthesis, expression and biological activity of the prohormone for gastrin releasing peptide (ProGRP)”. Endocrinology. 147 (1): 502–509. doi:10.1210/en.2005-0574. ISSN 0013-7227. PMID 16223866.}
  • ^{Saurin, Jc; Némoz-Gaillard, E; Ratineau, C; Chayvialle, Ja; Abello, J (2000). “Le neuropeptide bombésine module la prolifération et l’invasion tumorale”. Médecine/Sciences. 16 (8–9): 929. doi:10.4267/10608/1760. hdl:10608/1760. ISSN 1958-5381.} 
• It is also important to not confused with progastrin, consisting of 80 amino acids, precursor of gastrin in its intracellular version and oncogene in its extracellular version (hPG80).
  • ^{Verena, D. Huebner; Roulan, JiangS; Terry D., Lee; Kassu, Legesse; Takeshi, AzumiQ (April 2, 1990). Purification and Structural Characterization of Progastrin-derived Peptides from a Human Gastrinoma (PDF). THE JOURNAL OF BIOLOGICAL CHEMISTRY.}
  • ^{You, Benoit; Mercier, Frédéric; Assenat, Eric; Langlois-Jacques, Carole; Glehen, Olivier; Soulé, Julien; Payen, Léa; Kepenekian, Vahan; Dupuy, Marie; Belouin, Fanny; Morency, Eric (2020). “The oncogenic and druggable hPG80 (Progastrin) is overexpressed in multiple cancers and detected in the blood of patients”. EBioMedicine. 51: 102574. doi:10.1016/j.ebiom.2019.11.035. PMC 6938867. PMID 31877416.}

• The presence of GRP in lung cancer samples was identified in 1983.
  • ^{Bhatnagar, M.; Springall, D. R.; Ghatei, M. A.; Burnet, P. W. J.; Hamid, Q.; Giaid, A.; Ibrahim, N. B. N.; Cuttitta, F.; Spindel, E. R.; Penketh, R.; Rodek, C. (1988-07-01). “Localisation of mRNA and co-expression and molecular forms of GRP gene products in endocrine cells of fetal human lung”. Histochemistry. 90 (4): 299–307. doi:10.1007/BF00495974. ISSN 0301-5564. PMID 3068217. S2CID 12060289.} 
• In pathological situations, GRP has mitogenic activity in vitro in many tumors such as pancreatic, small cell lung (SCLC), prostate, kidney, breast and colorectal cancers.
  • ^{Uchida, Kazuhiro; Kojima, Akira; Morokawa, Nasa; Tanabe, Osamu; Anzai, Chieko; Kawakami, Makio; Eto, Yoshikatsu; Yoshimura, Kunihiko (2002-12-01). “Expression of progastrin-releasing peptide and gastrin-releasing peptide receptor mRNA transcripts in tumor cells of patients with small cell lung cancer”. Journal of Cancer Research and Clinical Oncology. 128 (12): 633–640. doi:10.1007/s00432-002-0392-8. ISSN 0171-5216. PMID 12474049. S2CID 23764903.}
  •  ^{Preston, Shaun R.; Miller, Glenn V.; Primrose, John N. (1996). “Bombesin-like peptides and cancer”. Critical Reviews in Oncology/Hematology. 23 (3): 225–238. doi:10.1016/1040-8428(96)00204-1. PMID 8842591.}
  •  ^{Moody, Terry W.; Chan, Daniel; Jensen, Jan Fahrenkrug and Robert T. (2003-01-31). “Neuropeptides as Autocrine Growth Factors in Cancer Cells”. Current Pharmaceutical Design. 9 (6): 495–509. doi:10.2174/1381612033391621. PMID 12570813. Retrieved 2020-08-03.}
  •  ^{Patel, Oneel; Dumesny, Chelsea; Giraud, Andrew S.; Baldwin, Graham S.; Shulkes, Arthur (2004). “Stimulation of proliferation and migration of a colorectal cancer cell line by amidated and glycine-extended gastrin-releasing peptide via the same receptor”. Biochemical Pharmacology. 68 (11): 2129–2142. doi:10.1016/j.bcp.2004.08.009. PMID 15498503.}
• GRP could operate as an autocrine growth factor. In cancers, GRP induces cell growth and inhibits apoptosis by shutting down the endoplasmic reticulum stress pathway.
  •  ^{Li, Xinqiu; Zhang, Litang; Ke, Xianzhu; Wang, Yuming (2013). “Human gastrin-releasing peptide triggers growth of HepG2 cells through blocking endoplasmic reticulum stress-mediated apoptosis”. Biochemistry (Moscow). 78 (1): 102–110. doi:10.1134/S0006297913010136. ISSN 0006-2979. PMID 23379566. S2CID 18293652.} 
• The mechanisms of the impacted signal pathways have not been established.
  •  ^{“Gastrin-releasing peptide gene-associated peptides are expressed in normal human fetal lung and small cell lung cancer: A novel peptide family found in man”. Lung Cancer. 5: 10. 1989. doi:10.1016/0169-5002(89)90319-x. ISSN 0169-5002.} 
• As early as 1994, research on Pro-GRP as a biomarker for small cell lung cancer began.
  • ^{“Pro-gastrin-releasing peptide (PROGRP) as a specific tumor marker in patients with small cell lung carcinoma (SCLC)”. Lung Cancer. 11: 45. 1994. doi:10.1016/0169-5002(94)93944-6. ISSN 0169-5002.} 
• Because of the very short half-life of GRP (2 minutes), the Pro-GRP is used for measurements and analysis. Since then, Pro-GRP has been used as a tumor marker for patients with small cell lung cancer (SCLC) in limited and extended stages.
  • ^{Cavalieri, Stefano; Morelli, Daniele; Martinetti, Antonia; Galli, Giulia; Nichetti, Federico; de Braud, Filippo; Platania, Marco (2018). “Clinical implications for pro-GRP in small cell lung cancer. A single center experience”. The International Journal of Biological Markers. 33 (1): 55–61. doi:10.5301/ijbm.5000305. ISSN 1724-6008. PMID 28967066.}

From Wikipedia where this page was last updated September 27, 2021

See also

• Pro-Gastrin-Releasing-Peptide
• Bombesin

Further reading

• Merali Z, McIntosh J, Anisman H (2000). “Role of bombesin-related peptides in the control of food intake”. Neuropeptides. 33 (5): 376–86. doi:10.1054/npep.1999.0054. PMID 10657515. S2CID 22270584.
• Baraniuk JN, Lundgren JD, Shelhamer JH, Kaliner MA (1992). “Gastrin releasing peptide (GRP) binding sites in human bronchi”. Neuropeptides. 21 (2): 81–4. doi:10.1016/0143-4179(92)90518-2. PMID 1557184. S2CID 40083693.
• Spindel ER, Zilberberg MD, Habener JF, Chin WW (1986). “Two prohormones for gastrin-releasing peptide are encoded by two mRNAs differing by 19 nucleotides”. Proc. Natl. Acad. Sci. U.S.A. 83 (1): 19–23. Bibcode:1986PNAS…83…19S. doi:10.1073/pnas.83.1.19. PMC 322782. PMID 3001723.
• Sausville EA, Lebacq-Verheyden AM, Spindel ER, et al. (1986). “Expression of the gastrin-releasing peptide gene in human small cell lung cancer. Evidence for alternative processing resulting in three distinct mRNAs”. J. Biol. Chem. 261 (5): 2451–7. doi:10.1016/S0021-9258(17)35956-2. PMID 3003116.
• Lebacq-Verheyden AM, Bertness V, Kirsch I, et al. (1987). “Human gastrin-releasing peptide gene maps to chromosome band 18q21”. Somat. Cell Mol. Genet. 13 (1): 81–6. doi:10.1007/BF02422302. PMID 3027901. S2CID 28347998.
• Naylor SL, Sakaguchi AY, Spindel E, Chin WW (1987). “Human gastrin-releasing peptide gene is located on chromosome 18”. Somat. Cell Mol. Genet. 13 (1): 87–91. doi:10.1007/BF02422303. PMID 3027902. S2CID 7514856.
• Lebacq-Verheyden AM, Kasprzyk PG, Raum MG, et al. (1989). “Posttranslational processing of endogenous and of baculovirus-expressed human gastrin-releasing peptide precursor”. Mol. Cell. Biol. 8 (8): 3129–35. doi:10.1128/MCB.8.8.3129. PMC 363540. PMID 3211139.
• Spindel ER, Chin WW, Price J, et al. (1984). “Cloning and characterization of cDNAs encoding human gastrin-releasing peptide”. Proc. Natl. Acad. Sci. U.S.A. 81 (18): 5699–703. Bibcode:1984PNAS…81.5699S. doi:10.1073/pnas.81.18.5699. PMC 391778. PMID 6207529.
• Benya RV, Kusui T, Pradhan TK, et al. (1995). “Expression and characterization of cloned human bombesin receptors”. Mol. Pharmacol. 47 (1): 10–20. PMID 7838118.
• Moody TW, Zia F, Venugopal R, et al. (1994). “Corticotropin-releasing factor stimulates cyclic AMP, arachidonic acid release, and growth of lung cancer cells”. Peptides. 15 (2): 281–5. doi:10.1016/0196-9781(94)90013-2. PMID 8008632. S2CID 44503352.
• Frankel A, Tsao MS, Viallet J (1994). “Receptor subtype expression and responsiveness to bombesin in cultured human bronchial epithelial cells”. Cancer Res. 54 (7): 1613–6. PMID 8137267.
• Lü F, Jin T, Drucker DJ (1996). “Proglucagon gene expression is induced by gastrin-releasing peptide in a mouse enteroendocrine cell line”. Endocrinology. 137 (9): 3710–6. doi:10.1210/en.137.9.3710. PMID 8756537.
• Bertenshaw GP, Turk BE, Hubbard SJ, et al. (2001). “Marked differences between metalloproteases meprin A and B in substrate and peptide bond specificity”. J. Biol. Chem. 276 (16): 13248–55. doi:10.1074/jbc.M011414200. PMID 11278902.
• Lambeir AM, Durinx C, Proost P, et al. (2001). “Kinetic study of the processing by dipeptidyl-peptidase IV/CD26 of neuropeptides involved in pancreatic insulin secretion”. FEBS Lett. 507 (3): 327–30. doi:10.1016/S0014-5793(01)02982-9. hdl:10067/366910151162165141. PMID 11696365. S2CID 26891876.
• Mason S, Smart D, Marshall IC, et al. (2002). “Identification and characterisation of functional bombesin receptors in human astrocytes”. Eur. J. Pharmacol. 438 (1–2): 25–34. doi:10.1016/S0014-2999(02)01268-2. PMID 11906707.
• Carroll RE, Matkowskyj K, Saunthararajah Y, et al. (2002). “Contribution of gastrin-releasing peptide and its receptor to villus development in the murine and human gastrointestinal tract”. Mech. Dev. 113 (2): 121–30. doi:10.1016/S0925-4773(02)00032-1. PMID 11960700. S2CID 15515339.
• Uchida K, Kojima A, Morokawa N, et al. (2003). “Expression of progastrin-releasing peptide and gastrin-releasing peptide receptor mRNA transcripts in tumor cells of patients with small cell lung cancer”. J. Cancer Res. Clin. Oncol. 128 (12): 633–40. doi:10.1007/s00432-002-0392-8. PMID 12474049. S2CID 23764903.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). “Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences”. Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Schneider J, Philipp M, Velcovsky HG, et al. (2003). “Pro-gastrin-releasing peptide (ProGRP), neuron specific enolase (NSE), carcinoembryonic antigen (CEA) and cytokeratin 19-fragments (CYFRA 21-1) in patients with lung cancer in comparison to other lung diseases”. Anticancer Res. 23 (2A): 885–93. PMID 12820318.

External links

• Gastrin-Releasing+Peptide at the US National Library of Medicine Medical Subject Headings (MeSH)
• Nosek, Thomas M. “Section 6/6ch2/s6ch2_35”. Essentials of Human Physiology. Archived from the original on 2016-03-24.

Peptides: neuropeptides

Hormones

Categories: 

• Genes on human chromosome 18
• Neurotransmitters

From Wikipedia where the main page was last updated August 25, 2022