Motilin

GI / Motility

Also known as: Motilin-22, MLN

GI Regulatory PeptidesResearch phase: Endogenous hormone (well characterized)Regulatory: Endogenous peptide. Not used clinically as a drug. Macrolide antibiotics (erythromycin) act as motilin agonists for gastroparesis treatment.

Mechanism

Motilin is the gut's housekeeper hormone — a 22-amino-acid peptide released cyclically during fasting to trigger the migrating motor complex (MMC), which sweeps food remnants and bacteria through the small intestine. This is the "stomach growling" signal. Erythromycin (the antibiotic) happens to activate the motilin receptor, which is why it is sometimes used to treat gastroparesis.

Technical detail

Motilin is a 22-amino-acid peptide released cyclically (~90-120 min intervals) from enteroendocrine Mo cells of the upper small intestine during fasting. It binds the motilin receptor (MLNR/GPR38), a Gq-coupled GPCR on smooth muscle cells and enteric neurons of the gastric antrum and duodenum, triggering Phase III of the migrating motor complex (MMC). Signaling involves PLC-IP3-Ca2+ release and cholinergic nerve activation. Erythromycin and other macrolides are motilin receptor agonists (motilides), explaining their prokinetic effects. Motilin is suppressed postprandially by nutrient ingestion.

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