motilin

Motilin is released cyclically from enteroendocrine M cells in the mucosa of the duodenum and jejunum during the interdigestive (fasting) period. It acts on motilin receptors (G protein-coupled receptors) located on smooth muscle cells and enteric neurons to initiate phase III of the migrating motor complex (MMC), a cyclic pattern of contractions that sweeps residual food, secretions, and debris from the stomach and small intestine toward the colon (the 'intestinal housekeeper'). Motilin release is inhibited by feeding and stimulated by fasting, vagal input, and certain nutrients. Its secretion is pulsatile, occurring roughly every 90-120 minutes during fasting, correlating with MMC cycles. Clinically, motilin physiology is important because erythromycin and other macrolide antibiotics act as motilin receptor agonists, which explains their prokinetic effects and common GI side effects (nausea, abdominal cramping, diarrhea). This property is therapeutically utilized in gastroparesis to enhance gastric emptying, though tachyphylaxis limits long-term use. Motilin also has diagnostic and research significance in understanding disorders of GI motility, such as diabetic gastroparesis, postoperative ileus, and irritable bowel syndrome. Novel motilin receptor agonists (motilides) have been investigated as alternatives to erythromycin for prokinetic therapy without antibiotic effects.