Neuropeptides intermediate
Gastrin-Releasing Peptide
A 27-amino acid neuropeptide that is the mammalian homolog of amphibian bombesin, regulating gastrin release, growth, and serving as a biomarker for small cell lung cancer.
By Encyclopeptide Editorial | 3 min read
GRP gastrin-releasing-peptide bombesin SCLC GI-physiology
Chemical Identity
| Property | Value |
|---|---|
| Name | Gastrin-Releasing Peptide |
| Gene | GRP (chromosome 18q21) |
| Sequence | Pro-Val-Lys-Val-Pro-Tyr-Gly-Gly-Gly-Thr-Ala-Val-Gly-His-Leu-Met-Ala-NH₂ |
| Length | 27 amino acids |
| Homology | 40% identical to amphibian bombesin |
| MW | 2785.2 Da |
| PDB Structures | 2C18 (NMR) |
Distribution
Central Nervous System
- Cortex: Widespread
- Hypothalamus: Paraventricular nucleus
- Hippocampus: Memory circuits
- Brainstem: Nucleus tractus solitarius
Peripheral
- GI tract: Gastric antrum, duodenum
- Lung: Neuroendocrine cells (Kulchitsky cells)
- Heart: Atria, ventricles
- Adrenal medulla
Receptor
Bombesin Receptor Subtype 2 (BB2/GRPR)
- Type: Class A G-protein coupled receptor
- Expression: GI tract, brain, lung, prostate
- G-protein: Gαq → PLC → IP₃ + DAG
Physiological Functions
GI Physiology
- Gastrin release: GRP stimulates G-cells → gastrin → gastric acid
- Pancreatic enzyme secretion: Stimulates exocrine pancreas
- GI motility: Modulates intestinal motility
Growth Promotion
- Mitogenic: Stimulates cell proliferation
- Autocrine loop in SCLC: Tumor produces GRP and GRPR
- Relevance: Potential oncogene in lung cancer
Other Functions
- CNS: Feeding, temperature regulation
- Cardiovascular: Blood pressure regulation
- Immune: Modulates immune cell function
Clinical Significance
Small Cell Lung Cancer (SCLC)
- Biomarker: Elevated serum GRP in SCLC
- Autocrine: SCLC cells produce GRP and express GRPR
- Therapeutic target: GRPR antagonists under investigation
Diagnostic Applications
- Serum GRP: SCLC biomarker (sensitivity ~60-80%)
- ⁶⁸Ga-GRPR PET: GRPR imaging for prostate cancer
- ¹⁷⁷Lu-GRPR: Radioligand therapy (investigational)
GRPR Antagonists
| Drug | Status | Indication |
|---|---|---|
| RC-3095 | Preclinical | Cancer |
| PD176252 | Research | Cancer |
| ⁶⁸Ga-NeoB | Clinical imaging | Prostate cancer |
| ¹⁷⁷Lu-NeoB | Phase I/II | Prostate cancer |
Manufacturing
- SPPS (Fmoc): Standard solid-phase synthesis
- C-terminal amidation: Required for activity
- Purification: RP-HPLC
- Characterization: Mass spectrometry, NMR
References
- McDonald TJ, et al. “Characterization of a gastrin releasing peptide from porcine non-antral gastric tissue.” Biochemical and Biophysical Research Communications 90:227-233, 1979. doi:10.1016/0014-5793(84)80718-5
- Spindel ER, et al. “Cloning and characterization of the bombesin/gastrin-releasing peptide receptor.” Science 249:806-810, 1990.
- Moody TW, et al. “GRP and its receptor in lung cancer.” Current Drug Targets 5:383-392, 2004.
- Reubi JC, et al. “Bombesin receptor antagonists: new tools for cancer imaging and therapy.” Journal of Nuclear Medicine 44:1709-1713, 2003.
- Berridge MJ. “Gastrin-releasing peptide: physiology and pharmacology.” Trends in Pharmacological Sciences 10:109-113, 1989.
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