Gastrin-releasing peptide

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
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2N0B, 2N0C, 2N0D, 2N0E, 2N0F, 2N0G, 2N0H
Identifiers
Aliases	GRP, BN, GRP-10, preproprogastrin releasing peptide
External IDs	OMIM: 137260; MGI: 95833; HomoloGene: 1580; GeneCards: GRP; OMA:GRP - orthologs
Gene location (Human) Chr. Chromosome 18 (human)[1] Band 18q21.32 Start 59,220,158 bp[1] End 59,230,774 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18 E1|18 38.98 cM Start 66,005,891 bp[2] End 66,019,667 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle gonad hair follicle gastric mucosa decidua cartilage tissue male germ cell sperm epithelium of lactiferous gland lactiferous duct Top expressed in subiculum lumbar subsegment of spinal cord suprachiasmatic nucleus barrel cortex ventral tegmental area hippocampus proper external carotid artery dentate gyrus of hippocampal formation granule cell embryo dorsomedial hypothalamic nucleus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function signaling receptor binding neuropeptide hormone activity Cellular component extracellular region extracellular space secretory granule lumen cytoplasmic vesicle Biological process neuropeptide signaling pathway signal transduction social behavior psychomotor behavior response to external biotic stimulus positive regulation of peptide hormone secretion positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway regulation of signaling receptor activity G protein-coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 18: 66.01 – 66.02 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]

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.

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]

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]