93755-85-2

Basic information

• Product Name: GASTRIN RELEASING PEPTIDE, HUMAN
• Synonyms: GRP (HUMAN);GRP;H-VAL-PRO-LEU-PRO-ALA-GLY-GLY-GLY-THR-VAL-LEU-THR-LYS-MET-TYR-PRO-ARG-GLY-ASN-HIS-TRP-ALA-VAL-GLY-HIS-LEU-MET-NH2;GASTRIN RELEASING AGENT, HUMAN;GASTRIN RELEASING PEPTIDE;GASTRIN RELEASING PEPTIDE, HUMAN;VAL-PRO-LEU-PRO-ALA-GLY-GLY-GLY-THR-VAL-LEU-THR-LYS-MET-TYR-PRO-ARG-GLY-ASN-HIS-TRP-ALA-VAL-GLY-HIS-LEU-MET-NH2;VPLPAGGGTVLTKMYPRGNHWAVGHLM-NH2
• CAS NO: 93755-85-2
• Molecular Formula: C130H204N38O31S2
• Molecular Weight: 2859.38
• Product Categories: Peptide;Neuromedins and related
• Mol File: 93755-85-2.mol
• Article Data: 0

Chemical Properties

• Appearance: /
• Density: 1.46±0.1 g/cm3(Predicted)
• Storage Temp.: −20°C
• CAS DataBase Reference: GASTRIN RELEASING PEPTIDE, HUMAN(CAS DataBase Reference)
• NIST Chemistry Reference: GASTRIN RELEASING PEPTIDE, HUMAN(93755-85-2)
• EPA Substance Registry System: GASTRIN RELEASING PEPTIDE, HUMAN(93755-85-2)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 93755-85-2(Hazardous Substances Data)

Usage

Description

Gastrin Releasing Peptide, Human (GRP) is a neuropeptide that plays a crucial role in the modulation of the autonomic system. It is an anorexigenic factor in the brain, regulates male sexual function at the spinal cord level, conveys the itch sensation, and is involved in various autonomic regulations in the brain. GRP also serves as a specific tumor marker for small cell lung cancer and has the GXHWAVGHLM amide (X=N or S) sequence at its C-terminus.

Uses

Used in Biomedical Research:
Gastrin Releasing Peptide, Human is used as a research tool for the absorption/neutralization of anti-GRP antibody prior to the tyramide signal amplification (TSA) procedure. This application aids in enhancing the detection and analysis of GRP in various biological samples, contributing to a better understanding of its role in physiological and pathological processes.

Discovery

First isolated from the porcine stomach and named gastrin-releasing peptide (GRP),1 GRP was originally believed to be a mammalian counterpart of the amphibian peptide, bombesin. Its structure has been determined in many mammals, including pigs, rats, mice, guinea pigs, dogs, and humans. In addition, GRP18–27, a possible fragment of mature GRP, was later isolated from the porcine spinal cord and originally called neuromedin C,2 although a more appropriate name is either GRP-10 or GRP18–27. GRP orthologs have been identified in birds, reptiles, amphibians, and teleost fish. On the other hand, it is reported that frogs have both GRP and bombesin, which are genetically distinct peptides, suggesting that GRP is not mammalian bombesin.

Structure

The human GRP precursor consists of 148 aa residues (rat, 147 aa). A predicted preproGRP translation product consists of a signal peptide, GRP1–27, and a C-terminal extended peptide termed proGRP31–125.?Most GRP peptides have a common sequence motif, GXHWAVGHLM amide (X=N or S), at their C-terminus. Although the N-terminal sequences are less conserved across vertebrate species, many identified GRP peptides in mammals consist of 27 aa residues, excluding rats and mice (29 aa). In nonmammals, the amphibian GRP peptide consists of 29 aa residues, the reptile peptide of 28 aa residues, and the avian peptide of 27 aa residues while the teleost peptide appears to be shorter (24–25 aa residues).

Gene, mRNA, and precursor

The human GRP gene is located on chromosome 18 (18q21.32), and consists of three exons (mRNA, 850 bp long ) . Its mRNA produces a 125-aa preproGRP precursor protein. In chickens, the grp gene is located on chromosome Z. In Xenopus, the grp gene is predicted to be located on chromosome 1. In zebrafish, the grp gene is predicted to be located on chromosome 21 (CH211-233A1).?GRP mRNA is produced in the CNS, stomach, intestine, pancreas, and lung in humans as well as other mammals. The expression of GRP mRNA is detected in the limbic system, including the amygdala as well as the hippocampus,8 and an overexpression in patients suffering from small cell lung cancer has been reported.

Synthesis and release

In the CNS, bombesin or GRP immunoreactivity was detected in approximately 5% of dorsal root ganglion neurons and approximately 10% of trigeminal ganglion neurons. In the brain, abundant GRP immunoreactivity was observed in the cerebral cortex, hypothalamus, and medulla oblongata. In the gastrointestinal tract, abundant GRP-immunoreactive fibers were observed in the stomach, suggesting gastrin release, and the small intestine, colon, and pancreas. In addition, the overexpression of GRP has been demonstrated at both the mRNA and protein levels in various types of tumors, including lung, prostate, breast, stomach, pancreas, and colon.

Receptors

GRPR is a GPCR superfamily with a seventransmembrane domain. GRPR is coupled to the Gq protein, and GRPR activation leads to an increase in intracellular Ca2+ and stimulation of the PLC/PKC and ERK/ MAPK pathways. In mammals, bombesin-like peptides act on a family of at least three GPCRs: the GRP-preferring receptor (GRPR), the neuromedin B-preferring receptor (NMBR), and the bombesin receptor subtype-3 (BRS-3), which is considered an orphan receptor at present. Human GRP binds GRPR (BB2 receptor) with a higher binding affinity (Ki of 1.8 - 0.4 nM) than that of NMBR (BB1 receptor) (Ki of 15 - 0.4 nM).

Biological functions

GRP functions via GRPR, which is highly expressed in the pancreas, and is also expressed in the stomach, adrenal cortex, and brain. Considerable evidence indicates that GRP plays a role in many physiological processes, including food intake, male sexual functions,circadian rhythms, sigh control, and fear-memory consolidation in the mammalian CNS. In addition, the itch sensation is a major biological function of GRP in mammals. In chicks, GRP functions as an anorexigenic factor in the brain.

Clinical implications

GRP and GRPR often excessively express in endocrinerelated cancer cells such as small cell lung cancer, prostate cancer, and gastrointestinal tract cancer. ProGRP is known to be a specific tumor marker for the small cell lung cancer because the half-life of proGRP in the circulation is much longer than that of GRP. GRPR is also important in prostate cancer growth and progression in an androgen-dependent manner.

Biochem/physiol Actions

GRP (gastrin releasing peptide) functions as an autocrine growth factor for nueroblastoma. It facilitates cell survival in PI3K/AKT (phosphatidylinositol-3-kinase/ v-Akt murine thymoma viral oncogene)-mediated manner and cell proliferation and angiogenesis in neuroblastoma. This peptide is involved in the release of gastrin and the control of gastric acid secretion and motor function. In patients with atopic dermatitis, the serum levels of this peptide are linked with pruritus.

Clinical Use

GRP mRNA is overexpressed in patients suffering from small cell lung cancer. Clinically, therefore, a higher level of circulating proGRP31–125 is a specific tumor marker for small cell lung cancer (higher than ~81.0 pg/mL in the plasma). In addition, intravenous infusions of GRP decrease spontaneous food intake in healthy men, suggesting GRP acts as a satiety signal in humans. GRP has not yet been used much clinically as a therapeutic agent.