Motilin receptor neuropharmacology: revised understanding

Although motilin was identified >40 years ago as a gastrointestinal hormone capable of stimulating gastric emptying, the relatively recent availability of molecular tools and focus on its neuronal activities are now clarifying mechanisms of action. In rodents, only motilin receptor pseudogenes are identified. In human stomach, facilitation of enteric cholinergic activity is identified as the main mechanism by which gastric emptying is increased; some motilin agonists act in a prolonged manner, contrasting with motilin itself and with studies using recombinant receptors. As such, assays using recombinant receptors seem poor predictors of in vivo activity. High-throughput screening enabled selective motilin agonists to be identified, which together with enhanced understanding into neuromuscular actions of motilin, promises to deliver rational treatments of disorders with delayed gastric emptying.

► Functional motilin activity is absent in rodents and pseudogenes are identified. ► Motilin and ghrelin receptors do not readily recognise each other's ligand. ► The predominant activity of motilin is to facilitate enteric cholinergic activity. ► Some motilin agonists cause prolonged facilitation of cholinergic activity. ► Selective motilin agonists with prolonged activity are available.