Gastrin-1: gut hormone that triggers stomach acid and digestion
A natural fragment of the gastrin hormone that signals the gut to release stomach acid and sense fullness; used only as a lab research tool.
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-1 is a 16-residue peptide derived from the human gastrin hormone family — a group of gut peptides that help coordinate digestion by signaling to the stomach and intestines. It acts at the cholecystokinin A receptor (CCKAR, also called CCK1R), a cell-surface receptor found mainly in the gallbladder and small intestine (Wang and colleagues, Genes 2020). Gastrin and its relatives are among the oldest signaling molecules in vertebrate biology: the CCK/gastrin family has been conserved across species since at least the emergence of cartilaginous fish, roughly 350 million years ago, pointing to its fundamental role in digestive physiology (Zeng and colleagues, Frontiers in Endocrinology 2020).
What it does
Gastrin-1 engages CCKAR to influence gastric acid output and gut motility. Through this receptor, gastrin signaling participates in regulating gallbladder contraction and small intestinal transit (Wang and colleagues, Genes 2020). The receptor also plays a role in the satiety axis: cholecystokinin and gastrin peptides acting at CCK1R contribute to appetite suppression signals sent from the gut to the brain (Miller and colleagues, Frontiers in Endocrinology 2021). Gastric acid secretion is separately modulated by other gut hormones such as ghrelin, which interact with the same secretory axis (Yakabi and colleagues, World Journal of Gastroenterology 2008). The peptide's biological activity depends critically on post-translational sulfation: tyrosine O-sulfation is a key determinant of receptor binding potency for CCK/gastrin family members, as established in mutational studies of the sulfation consensus sequence (Bundgaard and colleagues, Journal of Biological Chemistry 1997).
Evidence
- Human: Elevated gastrin levels (hypergastrinemia) are documented in clinical settings including gastrinoma and proton-pump inhibitor use; Niederle (Wiener klinische Wochenschrift 2007) reviewed its diagnosis and management. No interventional trials with Gastrin-1 as a therapeutic agent have been published.
- Animal: Knockout of the CCKAR gene in mice impairs gallbladder contraction and enhances cholesterol cholelithogenesis, demonstrating the receptor's role in biliary physiology (Wang and colleagues, Genes 2020).
- In vitro: Cryo-EM structural studies have resolved the architecture of CCK1R in complex with G-protein signaling partners; CCK1R couples to both Gs and Gq pathways (Ding and colleagues, Cell Discovery 2022).
Mechanism
CCKAR (CCK1R) is a class A G-protein-coupled receptor expressed predominantly in the gallbladder and small intestine. Upon ligand binding, the receptor engages both Gs and Gq signaling complexes, as revealed by cryo-EM structures of the receptor–G-protein assemblies (Ding and colleagues, Cell Discovery 2022). This dual coupling accounts for the range of downstream effects — from smooth muscle contraction to modulation of secretory activity — attributed to gastrin and CCK family peptides (Zeng and colleagues, Frontiers in Endocrinology 2020). Binding affinity within the gastrin/CCK family is strongly influenced by tyrosine sulfation: the O-sulfate group on tyrosine residues contributes directly to receptor recognition, and mutational analysis has defined the consensus features required for efficient sulfation (Bundgaard and colleagues, Journal of Biological Chemistry 1997). The stored 16-residue sequence (GPWLEEEEEAYGWMDF) represents the primary amino acid backbone; sulfation state of the tyrosine is not encoded in the raw sequence but is biologically relevant to receptor potency.
Known effects
- Gastric acid secretion — documented clinical relevance through hypergastrinemia syndromes (Niederle 2007); mechanistic role established
- Gallbladder contraction and biliary motility — loss-of-function (CCKAR knockout) evidence in mouse models (Wang and colleagues 2020)
- Appetite and satiety signaling — CCK1R agonism contributes to gut-to-brain satiety signaling; full CCK1R agonists have so far not succeeded in clinical weight-loss programs (Miller and colleagues 2021)
- Pancreatic enzyme release — implicated via CCK-B/CCK2R signaling in pancreatic biology (Zeng and colleagues 2020)
Safety signals
No safety or adverse-event data specific to Gastrin-1 as an administered peptide are available in the current literature set. Pathologically elevated endogenous gastrin (hypergastrinemia) is associated with gastric acid hypersecretion and is managed clinically through proton-pump inhibitor use and, where indicated, surgical intervention (Niederle 2007).
Regulatory status
- US: Not approved as a drug. Gastrin-1 is used as a research tool and in radiolabeled analog form for experimental tumor imaging (Roosenburg and colleagues, Amino Acids 2011).
- Therapeutic development: CCK1R-targeting agonists have been investigated as obesity treatments; as of the most recent review, full agonists of this receptor have not achieved clinical approval (Miller and colleagues 2021). Berna and colleagues (Current Opinion in Pharmacology 2007) reviewed the state of CCK/gastrin receptor ligand programs and therapeutic potential.
Related peptides
The gastrin/CCK family includes cholecystokinin, which shares the C-terminal tetrapeptide pharmacophore (–GWMDF or –WMDF) and competes at both CCK1R and CCK2R. See also the broader CCK receptor ligand landscape reviewed in Berna and colleagues (2007) and the structural biology of both receptor subtypes in Ding and colleagues (2022).
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 Gastrin-1 actually most active at the gastrin receptor (CCKBR) rather than the receptor a data record currently attaches to it?
Getting the receptor right matters because the gastrin receptor is tied to anxiety, chronic pain, and some cancers, so a mislabel could send research down the wrong path.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.8542965054512024 | boltz-2 |
| ranking score | 0.7629586458206177 | boltz-2 |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 1.191 | 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{pep10557,
sequence = {GPWLEEEEEAYGWMDF},
target = {cckar},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}