Storage Stability
Neuromedin C (NMC) is the C-terminal decapeptide (aa18-27) of gastrin-releasing peptide (GRP), produced by endoproteolytic processing in the GI tract and brain. It shares the same C-terminal sequence with bombesin (the amphibian prototype) and acts as a potent agonist at GRP receptors (GRPR/BB2), mediating food intake suppression, smooth muscle contraction, and neuroendocrine secretion.
Mechanism of Action
- Binds GRPR with high affinity (Kd ~1 nM), activating Gq/11/PLC/IP3 pathway and intracellular calcium mobilization
- Potently stimulates gastrin and cholecystokinin release from enteroendocrine cells, amplifying postprandial hormone responses
- GI smooth muscle: contracts circular muscle of stomach, small intestine, and colon via GRPR
- CNS: satiety-promoting; intracerebroventricular NMC suppresses food intake in rodents
- Mitogenic: GRPR activation by NMC stimulates proliferation in GRPR-expressing cancer cells
Research Findings
- NMC discovered as the active C-terminal fragment responsible for bombesin-like activity in GRP-processed tissues
- GRPR is overexpressed in prostate, breast, and colon cancers; NMC analogs used as tumor-targeting vectors for imaging and radiotherapy
- NMC suppressed food intake and gastric emptying more potently than full-length GRP in some rodent assays
- GRP/NMC system implicated in post-traumatic stress disorder; GRPR antagonism explored for anxiety reduction
- NMC analog [D-Phe6, beta-Ala11, Phe13, Nle14]bombesin(6-14) used as GRPR-targeting radioligand for PET imaging of prostate cancer
Research Protocols
- Food intake suppression: 1-10 nmol/kg IV or IP bolus in fasted rodents; compare vs GRP and bombesin
- In vitro GRPR activation: 1-100 nM NMC in GRPR-transfected cells; calcium mobilization or IP3 assay
- Pancreatic secretion: 1-3 pmol/kg/min IV infusion in dogs to stimulate enzyme secretion
- GRPR PET imaging: radiolabeled NMC analogs at 1-10 nmol injected for tumor localization in clinical trials
Interactions
- GRP: NMC is the C-terminal active fragment; longer GRP has same GRPR potency via same C-terminal sequence
- GRPR antagonists (RC-3095, PD 168368): block all NMC-mediated effects
- CCK and gastrin: NMC stimulates release of both; downstream amplification of satiety signaling
Safety Profile
Endogenous peptide fragment. Not used therapeutically at present. Pharmacological doses produce nausea, satiety, and GI smooth muscle contraction. GRPR antagonists (not NMC agonists) are the therapeutic direction for cancer and anxiety. Radioligand NMC analogs show acceptable safety in prostate cancer imaging.
Legal & Regulatory
Research peptide; not approved as therapeutic
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