Gastrin-14: gut hormone fragment that triggers stomach acid and digestion
A small piece of the hormone gastrin, made naturally in the stomach lining, that stimulates stomach acid, gallbladder contraction, and digestive enzyme release; used mainly as a lab research tool.
- Class
- Endogenous gastrointestinal peptide fragment (porcine)
- Status
- No approved therapeutic status identified in attached sources
- Main caveat
- No functional characterization, bioactivity data, or human evidence is attached to this card. The compiled source provides the porcine-origin sequence and a single molecular cloning reference only.
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
What this is
Gastrin-14 (also called minigastrin, or G-14) is a 14-amino-acid fragment of the hormone gastrin — one of the oldest known gut hormones, first identified as a chemical regulator of stomach acid in 1905. Like all active gastrins, it is produced by G cells in the stomach lining, where preprogastrin is processed down to smaller biologically active forms. The sequence stored here (WMEEEEEAYGWMDF) is derived from porcine (pig) preprogastrin, first cloned and sequenced by Yoo and colleagues (1982) — the active peptide carries a C-terminal amide (–NH₂) that is absent from the stored linear sequence but is essential for receptor binding. Gastrin-14 shares its entire bioactive C-terminal sequence with the larger G-17 and G-34 forms, making it the smallest naturally occurring gastrin fragment that retains the full biological activity of the parent hormone.
History
Gastrin was proposed as a blood-borne acid-stimulating signal from the stomach lining by John Edkins in 1905. The structural characterization of gastrin peptides was completed by Hilda Tracy and Roderic Gregory at the University of Liverpool in 1964, establishing the family of G-17 and G-34 forms. The molecular basis of porcine gastrin was resolved at the DNA level in 1982, when Yoo and colleagues cloned and sequenced full-length porcine preprogastrin cDNA (602 nucleotides encoding a 101-amino-acid precursor), confirming that the mature gastrin sequence is located near the carboxyl end of preprogastrin and flanked by paired basic amino acid residues that mark the proteolytic cleavage sites (Yoo and colleagues 1982). Gastrin-14 (the 14-amino-acid C-terminal fragment, also called minigastrin) was recognized as the shortest naturally occurring form that preserves the complete biological activity of the gastrin family. The CCK/gastrin receptor family was further characterized by Berna and colleagues (2007) in a review of ligands targeting these receptors for therapeutic development.
What it does
Gastrin-14 stimulates gastric acid secretion, promotes gastric mucosal growth, and triggers pancreatic enzyme release and gallbladder emptying — the classical functions of the gastrin hormone family. Its physiological action is primarily mediated through the cholecystokinin-2 receptor (CCK2R, also called the gastrin receptor or CCK-B receptor), a class A GPCR that couples preferentially to Gq and is expressed on enterochromaffin-like (ECL) cells in the oxyntic mucosa, on gastric parietal cells, and on pancreatic cells (Zeng and colleagues 2020). Gastrin-14 acts by binding CCK2R on ECL cells, inducing histamine release, which in turn drives parietal cell acid secretion — the dominant mechanism of gastrin-stimulated acid output. The peptide also promotes proliferation of gastric mucosal epithelium and chief cell pepsinogen secretion.
The C-terminal tetrapeptide amide (Trp-Met-Asp-Phe-NH₂) shared between gastrin and cholecystokinin is the minimal bioactive pharmacophore: this motif docks into the transmembrane binding pocket of CCK2R, and the terminal amide is required for high-affinity binding (Zeng and colleagues 2020; Ding and colleagues 2022). All naturally occurring C-terminally amidated gastrin forms — G-14, G-17, G-34 — carry this motif and are equipotent at CCK2R; they differ in circulating half-life and in amino-terminal extension, not in intrinsic receptor efficacy.
Gastrin-14 has poor affinity for the cholecystokinin-1 receptor (CCK1R/CCKAR), which recognizes sulfated CCK peptides with 500–1000-fold higher affinity and potency than gastrin (Zeng and colleagues 2020). The satiety-signaling, gallbladder contraction, and pancreatic enzyme secretion effects ascribed to the CCK receptor family in the gut are predominantly CCK1R-mediated for CCK itself; gastrin's contribution to gallbladder and pancreatic physiology is primarily through CCK2R at pharmacological concentrations (Miller and colleagues 2021).
Evidence
- Human: Gastrin-14 has been used as a research tool and pharmacological probe in studies of gastric acid physiology, but no dedicated clinical trials for gastrin-14 as a therapeutic agent are registered on ClinicalTrials.gov. The broader gastrin biology has been characterized in humans through clinical research on gastrinoma (Zollinger-Ellison syndrome), gastric physiology, and gastric cancer risk associated with hypergastrinaemia (Zeng and colleagues 2020).
- Animal: Studies in knockout mouse models of CCK1R and CCK2R have dissected the respective contributions of the two receptors to gastric acid secretion and gallbladder function. CCKAR knockout in mice enhances cholesterol gallstone formation by impairing gallbladder contractility, establishing CCKAR as an important gallstone gene (Lith13) (Wang and colleagues 2020).
- In vitro: Cryo-EM structural work by Ding and colleagues (2022) resolved the CCK2R–Gq signaling complex liganded with gastrin-17, revealing the structural basis for CCK2R selectivity: the gastrin C-terminal sequence lodges in the transmembrane binding pocket, and a charge-distinct sulfation-sensing pocket distinguishes CCK1R from CCK2R. These data directly apply to gastrin-14, which carries the identical binding pharmacophore.
Mechanism
Gastrin-14 activates CCK2R, a class A GPCR. Upon binding, CCK2R couples to Gq to activate phospholipase C (PLC), generating inositol trisphosphate (IP₃) and diacylglycerol (DAG), which raises intracellular calcium and activates protein kinase C. On gastric ECL cells, this triggers histamine synthesis and secretion; the released histamine then activates H₂ receptors on adjacent parietal cells to drive HCl secretion into the gastric lumen (Zeng and colleagues 2020). On parietal cells themselves, CCK2R activation by gastrin can also directly stimulate acid secretion, although the indirect ECL–histamine route is considered dominant under physiological conditions.
The structural selectivity of CCK2R for the gastrin C-terminal sequence was visualized by Ding and colleagues (2022): CCK1R requires the extended heptapeptide amide of CCK including a sulfated tyrosine in position 7 from the C-terminus, while CCK2R recognizes the shorter tetrapeptide amide (WMDF-NH₂) shared between CCK and gastrin, with no sulfation requirement. This distinction explains why gastrin-14 is a potent CCK2R agonist but a poor CCK1R ligand.
The stored sequence WMEEEEEAYGWMDF is the linear backbone; the biologically active form requires C-terminal amidation (–NH₂). Non-amidated gastrin forms (glycine-extended intermediates produced during biosynthetic processing) have markedly reduced potency at CCK2R and are considered processing intermediates rather than active signaling molecules (Zeng and colleagues 2020).
Known effects
- Gastric acid secretion — Well-established in gastric physiology; the core function of the gastrin hormone family. Mediated via CCK2R on ECL cells and parietal cells.
- Gastric mucosal growth — Gastrin drives proliferation of the oxyntic gastric epithelium; ECL cell hyperplasia and parietal cell expansion are downstream consequences of sustained CCK2R stimulation (Zeng and colleagues 2020).
- Pancreatic and gallbladder effects — Present at pharmacological concentrations via CCK2R; the dominant physiological driver of gallbladder contraction and pancreatic enzyme secretion is CCK acting at CCK1R rather than gastrin-14 at CCK2R (Miller and colleagues 2021).
- Gastric motility — Gastrin increases antral muscle contractions and facilitates gastric emptying at physiological concentrations.
Safety signals
No clinical safety profile is established for gastrin-14 as an isolated peptide; safety data come from the wider gastrin biology in disease contexts. Chronic hypergastrinaemia (elevated endogenous gastrin, as in Zollinger-Ellison syndrome or following prolonged proton-pump inhibitor use) is associated with ECL cell hyperplasia and, in sustained cases, with increased gastric carcinoid risk (Zeng and colleagues 2020). These effects are mediated by the same CCK2R pathway activated by gastrin-14.
Regulatory status
- US: Not approved by the FDA. No IND or NDA on record for gastrin-14 as a therapeutic. Research-use compound only.
- EU: Not approved by the EMA.
- WADA: Not listed as a prohibited substance.
Related peptides
Gastrin-14 is the 14-residue C-terminal fragment of the gastrin family. The larger forms — gastrin-17 (G-17, "little gastrin") and gastrin-34 (G-34, "big gastrin") — share the identical bioactive pharmacophore and differ primarily in circulating half-life. Cholecystokinin, the paralog that acts primarily via CCK1R, shares the same C-terminal tetrapeptide amide sequence with gastrin and is the principal mediator of satiety, gallbladder contraction, and pancreatic enzyme secretion through peripheral CCK1R on vagal afferent neurons.
See also: Secretin — the gastrointestinal hormone that functionally counterbalances gastrin by inhibiting gastric acid secretion in response to duodenal acidification, and stimulates pancreatic bicarbonate secretion.
Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.
Is the official receptor target for this peptide mis-annotated in databases?
If true, drug developers and researchers using this entry would be pointed to the correct biological target, potentially improving the accuracy of peptic ulcer and acid-reflux drug programs. Patients in those programs could benefit from better-targeted therapies.
Could a simplified, stable version of this stomach peptide nudge the pancreas into making new insulin-producing cells?
If true, people with type 1 diabetes might benefit from a new class of regenerative drugs that could reduce or eliminate insulin dependence. It could also open a path to smaller, easier-to-manufacture drugs compared with larger gastrin forms.
If the five glutamates in this peptide are replaced with a synthetic chemical that does the same structural job but resists digestion, would the peptide still work and last longer in the body?
If true, this approach could convert an unstable natural peptide into a viable drug candidate for stomach disorders or diabetes therapies, potentially enabling oral delivery and reducing how often patients need to take it.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.9101929664611816 | boltz-2 |
| ranking score | 0.8206619620323181 | boltz-2 |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.988 | global PDE — lower = better |
| disorder | NaN | fraction disordered |
▸3-letter notation
▸recipeboltz-2 1.0
| parameter | value |
|---|---|
| model | boltz-2 1.0 |
| weights | — |
| hardware | nvidia_nim_api |
| mlx version | — |
| python | — |
| random seed | — |
| msa strategy | none |
| diffusion samples | 1 |
| runtime | — |
| predicted by | mlx@peptide |
| predicted at | 2026-04-24 |
▸citationbibtex
@peptide{pep10685,
sequence = {WMEEEEEAYGWMDF},
target = {cckar},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}