Gastrin-releasing peptide explained

Gastrin-releasing peptide GRP, is a neuropeptide, a regulatory molecule encoded in the human by the GRP gene. GRP 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.

GRP encodes a number of bombesin-like peptides.^{[1] [2] [3] [4]} Its 148-amino acid preproprotein, 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.^[5] 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.^[1]

Function

Gastrin-releasing peptide is a regulatory human peptide that elicits gastrin release and regulates gastric acid secretion and enteric motor function.^[6] 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.^[7]

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

GRP is located on chromosome 18q21. PreproGRP (the unprocessed form of GRP) is encoded in three exons separated by two introns.^[4] Alternative splicing results in multiple transcript variants encoding different isoforms.^[1]

Synthesis

PreproGRP begins with signal peptidase cleavage to generate the pro-gastrin-releasing-peptide (proGRP), which is then processed by proteolytic cleavages, to form smaller GRP peptides.^[6]

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.^[6]

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.^[1]

Further reading

• Merali Z, McIntosh J, Anisman H . Role of bombesin-related peptides in the control of food intake . Neuropeptides . 33 . 5 . 376–86 . 2000 . 10657515 . 10.1054/npep.1999.0054 . 22270584 .
• Baraniuk JN, Lundgren JD, Shelhamer JH, Kaliner MA . Gastrin releasing peptide (GRP) binding sites in human bronchi . Neuropeptides . 21 . 2 . 81–4 . 1992 . 1557184 . 10.1016/0143-4179(92)90518-2 . 40083693 .
• Spindel ER, Zilberberg MD, Habener JF, Chin WW . 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 . 1986 . 3001723 . 10.1073/pnas.83.1.19 . 322782. 1986PNAS...83...19S . free .
• Sausville EA, Lebacq-Verheyden AM, Spindel ER, etal . 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 . 1986 . 10.1016/S0021-9258(17)35956-2 . 3003116 . free .
• Lebacq-Verheyden AM, Bertness V, Kirsch I, etal . Human gastrin-releasing peptide gene maps to chromosome band 18q21 . Somat. Cell Mol. Genet. . 13 . 1 . 81–6 . 1987 . 3027901 . 10.1007/BF02422302 . 28347998 .
• Naylor SL, Sakaguchi AY, Spindel E, Chin WW . Human gastrin-releasing peptide gene is located on chromosome 18 . Somat. Cell Mol. Genet. . 13 . 1 . 87–91 . 1987 . 3027902 . 10.1007/BF02422303 . 7514856 .
• Lebacq-Verheyden AM, Kasprzyk PG, Raum MG, etal . Posttranslational processing of endogenous and of baculovirus-expressed human gastrin-releasing peptide precursor . Mol. Cell. Biol. . 8 . 8 . 3129–35 . 1989 . 3211139 . 10.1128/MCB.8.8.3129. 363540.
• Spindel ER, Chin WW, Price J, etal . Cloning and characterization of cDNAs encoding human gastrin-releasing peptide . Proc. Natl. Acad. Sci. U.S.A. . 81 . 18 . 5699–703 . 1984 . 6207529 . 10.1073/pnas.81.18.5699 . 391778. 1984PNAS...81.5699S . free .
• Benya RV, Kusui T, Pradhan TK, etal . Expression and characterization of cloned human bombesin receptors . Mol. Pharmacol. . 47 . 1 . 10–20 . 1995 . 7838118 .
• Moody TW, Zia F, Venugopal R, etal . Corticotropin-releasing factor stimulates cyclic AMP, arachidonic acid release, and growth of lung cancer cells . Peptides . 15 . 2 . 281–5 . 1994 . 8008632 . 10.1016/0196-9781(94)90013-2 . 44503352 .
• Frankel A, Tsao MS, Viallet J . Receptor subtype expression and responsiveness to bombesin in cultured human bronchial epithelial cells . Cancer Res. . 54 . 7 . 1613–6 . 1994 . 8137267 .
• Lü F, Jin T, Drucker DJ . Proglucagon gene expression is induced by gastrin-releasing peptide in a mouse enteroendocrine cell line . Endocrinology . 137 . 9 . 3710–6 . 1996 . 8756537 . 10.1210/en.137.9.3710 . free .
• Bertenshaw GP, Turk BE, Hubbard SJ, etal . Marked differences between metalloproteases meprin A and B in substrate and peptide bond specificity . J. Biol. Chem. . 276 . 16 . 13248–55 . 2001 . 11278902 . 10.1074/jbc.M011414200 . free .
• Lambeir AM, Durinx C, Proost P, etal . Kinetic study of the processing by dipeptidyl-peptidase IV/CD26 of neuropeptides involved in pancreatic insulin secretion . FEBS Lett. . 507 . 3 . 327–30 . 2001 . 11696365 . 10.1016/S0014-5793(01)02982-9 . 10067/366910151162165141 . 26891876 . free .
• Mason S, Smart D, Marshall IC, etal . Identification and characterisation of functional bombesin receptors in human astrocytes . Eur. J. Pharmacol. . 438 . 1–2 . 25–34 . 2002 . 11906707 . 10.1016/S0014-2999(02)01268-2 .
• Carroll RE, Matkowskyj K, Saunthararajah Y, etal . Contribution of gastrin-releasing peptide and its receptor to villus development in the murine and human gastrointestinal tract . Mech. Dev. . 113 . 2 . 121–30 . 2002 . 11960700 . 10.1016/S0925-4773(02)00032-1 . 15515339 . free .
• Uchida K, Kojima A, Morokawa N, etal . 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 . 2003 . 12474049 . 10.1007/s00432-002-0392-8 . 23764903 .
• Strausberg RL, Feingold EA, Grouse LH, etal . 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 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241. 2002PNAS...9916899M . free .
• Schneider J, Philipp M, Velcovsky HG, etal . 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 . 2003 . 12820318 .

External links

• • Book: Nosek, Thomas M. . Essentials of Human Physiology. Section 6/6ch2/s6ch2_35 . http://humanphysiology.tuars.com/program/section6/6ch2/s6ch2_35.htm . https://web.archive.org/web/20160324124828/http://humanphysiology.tuars.com/program/section6/6ch2/s6ch2_35.htm. 2016-03-24.

Notes and References

1. Web site: Entrez Gene: GRP gastrin-releasing peptide.
2. Spindel ER, Chin WW, Price J, Rees LH, Besser GM, Habener JF . Cloning and characterization of cDNAs encoding human gastrin-releasing peptide . Proc. Natl. Acad. Sci. U.S.A. . 81 . 18 . 5699–703 . September 1984 . 6207529 . 391778 . 10.1073/pnas.81.18.5699. 1984PNAS...81.5699S . free .
3. Spindel ER, Zilberberg MD, Habener JF, Chin WW . 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 . January 1986 . 3001723 . 322782 . 10.1073/pnas.83.1.19. 1986PNAS...83...19S . free .
4. Lebacq-Verheyden AM, Bertness V, Kirsch I, Hollis GF, McBride OW, Battey J . Human gastrin-releasing peptide gene maps to chromosome band 18q21 . Somat. Cell Mol. Genet. . 13 . 1 . 81–6 . January 1987 . 3027901 . 10.1007/BF02422302. 28347998 .
5. Web site: Neuromedin C . pubchem.ncbi.nlm.nih.gov . en.
6. Merali Z, McIntosh J, Anisman H . Role of bombesin-related peptides in the control of food intake . Neuropeptides . 33 . 5 . 376–86 . October 1999 . 10657515 . 10.1054/npep.1999.0054 . 22270584 .
7. Antle . Michael C. . Silver . Rae . March 2005 . Orchestrating time: arrangements of the brain circadian clock . Trends in Neurosciences . 28 . 3 . 145–151 . 10.1016/j.tins.2005.01.003 . 0166-2236.