Motilin Receptor

The motilin receptor is a Gq/11-protein-coupled receptor that mediates progastrokinetic effects. The motilin receptor promotes gastric emptying after food intake and increases smooth muscle contraction in the GI tract.

ANQ 11125
MA 2029
GSK 962040


An Overview of Motilin Receptor

The motilin receptor, a new kind of G-protein-coupled receptor, helps to achieve the function of motilin. In 1997, the motilin receptor was named GPR38 and also called “orphan receptor”. In 1999, Feighner and his colleagues cloned and identified the “orphan receptor” as the motilin receptor. The motilin is a peptide composed of 22 amino acids that is expressed primarily in upper gastrointestinal tract of most mammals and regulates a premature phase Ⅲ of the migrating motor complex. In vitro experiments demonstrated that motilin stimulates the contraction of isolated smooth muscle strips in human and rabbits by directly acting on the motilin receptors of smooth muscle cells.

Antagonists/Agonists of Motilin Receptor

Erythromycin is the most known motilin receptor agonist, blocking intestinal neuromuscular functions at similar concentration by activating motilin receptors. Erythromycin is able to increase low esophageal pressure and inhibit postprandial gastroesophageal reflux. Scientists have conducted experiments on animals to predict the functions of motilin receptor antagonists/agonists. In rabbits, the motilin receptor antagonists inhibited gastrointestinal contraction and visceral pain caused by motilin. It is reported that motilin receptor agonists promoted gastrointestinal motility in human and rabbits, and treated gastric emptying disorders in patients with diabetic gastroparesis or non-diabetic gastroparesis. In 2007, McCallum found that the motilin receptor agonists could relieve gastric emptying delay and diabetic gastroparesis.

Motilin Receptor and Diseases

Ter Beek et al confirmed that the motilin receptor was distributed in the muscular layer and mucosal layer of the stomach, duodenum, ileum in normal people and the expression of motilin receptor in patients with inflammatory bowel disease is slightly higher than that of the normal group. Kollmar et al. studied the expression of motilin receptors and gastric emptying of patients after pancreatoduodenectomy, and found that the incidence of delayed gastric emptying was reduced after surgery because the operation retained the jejunal segment with high motilin receptors distribution density. At present, the motilin receptor antagonists/agonists have been gradually applied into clinical use due to the function of motilin receptors in these diseases.


1. Sanger, G. J. (2014). Ghrelin and motilin receptor agonists: time to introduce bias into drug design. Neurogastroenterology & Motility, 26(2), 149-155.

2. Sanger, G. J. (2012). Motilin receptor neuropharmacology: revised understanding. Current opinion in pharmacology, 12(6), 641-646.

3. Deloose, E., Depoortere, I., de Hoon, J., Van Hecken, A., Dewit, O. E., Vasist Johnson, L. S., ... & Tack, J. (2018). Manometric evaluation of the motilin receptor agonist camicinal (GSK 962040) in humans. Neurogastroenterology & Motility, 30(1), e13173.