Motilin Receptor

Motilin is a gastrointestinal hormone produced in the small intestine; during the fasting state, plasma levels of motilin fluctuate and induce gastric contractionsto signal hunger via a cholinergic pathway. The orphan G protein-coupled receptor GPR38, originally isolated from the thyroid gland, was identified as the motilin receptor in 1999.  Two alternatively spliced forms of this receptor exist: GPR38A is the typical (seven transmembrane domains) biologically active form; GPR38B is a truncated (five transmembrane domains) biologically inactive form. The motilin receptor is structurally related to the ghrelin receptor (overall amino acid identity 51.6%), neurotensin receptor 1 (32.7%), neurotensin receptor 2 (34.1%) and the orphan GPR39 receptor (28.7%). Motilin receptor density in humans is highest in the gastroduodenal region and decreases distally. By contrast, the highest motilin receptor density in rabbits is found in the colon.  The motilin receptor is susceptible to desensitization. The phosphorylated motilin receptor recruits β-arrestin 2 with greater affinity than β-arrestin 1. These multifunctional adaptor proteins bind to the phosphorylated receptor and disrupt the interaction between the receptor and G proteins to target the receptor to clathrin-coated pits.


1.Deloose E, et al. Nat Rev Endocrinol. 2019;15(4):238–250.