Gastrin-releasing peptide

Last updated
GRP
GRP .png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases GRP , BN, GRP-10, preproprogastrin releasing peptide
External IDs OMIM: 137260 MGI: 95833 HomoloGene: 1580 GeneCards: GRP
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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

Gastrin-releasing peptideGRP, 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.

Contents

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.

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]

Related Research Articles

<span class="mw-page-title-main">Gastrin</span> Mammalian protein found in Homo sapiens

Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas.

Bombesin is a 14-amino acid peptide originally isolated from the skin of the European fire-bellied toad by Vittorio Erspamer et al. and named after its source. It has two known homologs in mammals called neuromedin B and gastrin-releasing peptide. It stimulates gastrin release from G cells. It activates three different G-protein-coupled receptors known as BBR1, -2, and -3. It also activates these receptors in the brain. Together with cholecystokinin, it is the second major source of negative feedback signals that stop eating behaviour.

Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second messenger signaling cascade that induces a broad, long-lasting signal. This modulation can last for hundreds of milliseconds to several minutes. Some of the effects of neuromodulators include: altering intrinsic firing activity, increasing or decreasing voltage-dependent currents, altering synaptic efficacy, increasing bursting activity and reconfigurating synaptic connectivity.

<span class="mw-page-title-main">Neurotensin</span> Chemical compound

Neurotensin is a 13 amino acid neuropeptide that is implicated in the regulation of luteinizing hormone and prolactin release and has significant interaction with the dopaminergic system. Neurotensin was first isolated from extracts of bovine hypothalamus based on its ability to cause a visible vasodilation in the exposed cutaneous regions of anesthetized rats.

Neuromedin B (NMB) is a bombesin-related peptide in mammals. It was originally purified from pig spinal cord, and later shown to be present in human central nervous system and gastrointestinal tract.

<span class="mw-page-title-main">Bombesin-like receptor 3</span> Protein-coding gene in humans

The bombesin receptor subtype 3 also known as BRS-3 or BB3 is a protein which in humans is encoded by the BRS3 gene.

<span class="mw-page-title-main">Neuromedin B receptor</span> Protein-coding gene in the species Homo sapiens

The neuromedin B receptor (NMBR), now known as BB1 is a G protein-coupled receptor whose endogenous ligand is neuromedin B. In humans, this protein is encoded by the NMBR gene.

<span class="mw-page-title-main">Gastrin-releasing peptide receptor</span> Protein-coding gene in the species Homo sapiens

The gastrin-releasing peptide receptor (GRPR), now properly known as BB2 is a G protein-coupled receptor whose endogenous ligand is gastrin releasing peptide. In humans it is highly expressed in the pancreas and is also expressed in the stomach, adrenal cortex and brain.

<span class="mw-page-title-main">Prolactin-releasing peptide receptor</span> Protein-coding gene in the species Homo sapiens

The prolactin-releasing peptide receptor (PrRPR) also known as G-protein coupled receptor 10 (GPR10) is a protein that in humans is encoded by the PRLHR gene.

<span class="mw-page-title-main">P2RY2</span> Protein-coding gene in the species Homo sapiens

P2Y purinoceptor 2 is a protein that in humans is encoded by the P2RY2 gene.

<span class="mw-page-title-main">Somatostatin receptor 5</span> Protein-coding gene in the species Homo sapiens

Somatostatin receptor type 5 is a protein that in humans is encoded by the SSTR5 gene.

<span class="mw-page-title-main">Neuropeptide FF receptor 2</span> Protein-coding gene in the species Homo sapiens

Neuropeptide FF receptor 2, also known as NPFF2 is a human protein encoded by the NPFFR2 gene.

<span class="mw-page-title-main">Trefoil factor 3</span> Protein-coding gene in the species Homo sapiens

Trefoil factor 3 is a protein that in humans is encoded by the TFF3 gene.

<span class="mw-page-title-main">TAC3</span> Protein-coding gene in the species Homo sapiens

Tachykinin-3 is a protein that in humans is encoded by the TAC3 gene.

<span class="mw-page-title-main">RCP9</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerase III subunit RPC9 is an enzyme that in humans is encoded by the CRCP gene.

<span class="mw-page-title-main">TAC1</span> Protein-coding gene in humans

Preprotachykinin-1,, is a precursor protein that in humans is encoded by the TAC1 gene.

<span class="mw-page-title-main">TAC4</span> Protein-coding gene in the species Homo sapiens

Tachykinin-4 is a protein that in humans is encoded by the TAC4 gene.

Bombesin-like peptides comprise a large family of peptides which were initially isolated from amphibian skin, where they stimulate smooth muscle contraction. They were later found to be widely distributed in mammalian neural and endocrine cells.

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. 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).

Progastrin is an 80-amino acid intracellular protein and the precursor of gastrin, a gastrointestinal hormone produced by G cells in the gastric antrum. The main function of gastrin is to regulate acid secretion. During digestion, only gastrin is released into the bloodstream and stimulates the secretion of hydrochloric acid in the stomach as well as pancreatic digestive enzymes. In humans, progastrin is encoded by the GAST gene. Progastrin is expressed primarily in stomach tissue.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000134443 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 3 4 "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". 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.
  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". 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.
  8. 1 2 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.
  9. "Neuromedin C". pubchem.ncbi.nlm.nih.gov.
  10. 1 2 3 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.

Further reading