Gastrin-releasing peptide

GRP
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesGRP, BN, GRP-10, preproprogastrin releasing peptide
External IDsOMIM: 137260; MGI: 95833; HomoloGene: 1580; GeneCards: GRP; OMA:GRP - orthologs
Orthologs
SpeciesHumanMouse
Entrez

2922

225642

Ensembl

ENSG00000134443

ENSMUSG00000024517

UniProt

P07492

Q8R1I2

RefSeq (mRNA)

NM_001012512
NM_001012513
NM_002091

NM_175012

RefSeq (protein)

NP_002082
NP_001012531
NP_001012530

NP_778177

Location (UCSC)Chr 18: 59.22 – 59.23 MbChr 18: 66.01 – 66.02 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5][6][7][8] 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.[9] 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.[5]

Gene

GRP is located on chromosome 18q21. PreproGRP (the unprocessed form of GRP) is encoded in three exons separated by two introns.[8] Alternative splicing results in multiple transcript variants encoding different isoforms.[5]

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.[10]

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.[10]

Function

Gastrin-releasing peptide is a regulatory human peptide that elicits gastrin release and regulates gastric acid secretion and enteric motor function.[10] 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.[11]

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.

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.[5]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000134443 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024517 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c d "Entrez Gene: GRP gastrin-releasing peptide".
  6. ^ Spindel ER, Chin WW, Price J, Rees LH, Besser GM, Habener JF (September 1984). "Cloning and characterization of cDNAs encoding human gastrin-releasing peptide". Proceedings of the National Academy of Sciences of the United States of America. 81 (18): 5699–5703. Bibcode:1984PNAS...81.5699S. doi:10.1073/pnas.81.18.5699. PMC 391778. PMID 6207529.
  7. ^ 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". Proceedings of the National Academy of Sciences of the United States of America. 83 (1): 19–23. Bibcode:1986PNAS...83...19S. doi:10.1073/pnas.83.1.19. PMC 322782. PMID 3001723.
  8. ^ a b 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". Somatic Cell and Molecular Genetics. 13 (1): 81–86. doi:10.1007/BF02422302. PMID 3027901. S2CID 28347998.
  9. ^ "Neuromedin C". pubchem.ncbi.nlm.nih.gov.
  10. ^ a b c Merali Z, McIntosh J, Anisman H (October 1999). "Role of bombesin-related peptides in the control of food intake". Neuropeptides. 33 (5): 376–386. doi:10.1054/npep.1999.0054. PMID 10657515. S2CID 22270584.
  11. ^ Antle MC, Silver R (March 2005). "Orchestrating time: arrangements of the brain circadian clock". Trends in Neurosciences. 28 (3): 145–151. doi:10.1016/j.tins.2005.01.003. ISSN 0166-2236. PMID 15749168.

Further reading

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