A Review on Motilin: Functioning Cellular and Molecular Mechanism, Pathology and Clinical Significance

Abstract: The discovery of the motilin receptor and advances in techniques warrant a reevaluation of motilin's digestive role. Despite similarities with ghrelin in genomic structure and gastrointestinal effects, motilin and ghrelin receptors are specific and do not cross-react. In rodents, motilin's function is limited due to receptor pseudogenes. While motilin stimulates enteric cholinergic activity rather than directly contracting muscle, its effects differ from the more prolonged impact of agonists like erythromycin and GSK962040. Furthermore, while motilin’s receptor is highly expressed in muscle tissue, motilin primarily acts by promoting enteric cholinergic activity rather than directly inducing muscle contraction. The use of erythromycin, an antibiotic, as a motilin receptor agonist to accelerate gastric emptying in patients has raised safety concerns, particularly regarding the potential for increased antibiotic resistance. Motilide substitutes have not been successful, but new non-motilide small-molecule agonists are in trials for conditions like diabetic gastroparesis. This underscores the importance of balancing artificial models, structural data, and animal studies in pharmacology. In conclusion, the study of motilin and its receptor provides an important example for translational pharmacologists, emphasizing the need to avoid overreliance on artificial systems, structural data, and animal models when developing new therapeutic approaches. The complexities of motilin's actions and the challenges associated with receptor agonism highlight the importance of continued research and innovation in the field of gastrointestinal pharmacology.