Human motilin receptor (MTLR)

The **human motilin receptor** is a **class A G protein-coupled receptor (GPCR)** encoded by the MLNR gene, expressed primarily on smooth muscle cells and enteric neurons of the stomach, small intestine, and colon[1][2][3][8][6][7]. Its activation by the peptide hormone motilin, or by certain drugs such as erythromycin, induces phase III contractions of the **migrating motor complex (MMC)**, regulating interdigestive gastric and intestinal motility[1][3][5][8]. The receptor consists of 412 amino acids with seven transmembrane domains; its N-terminus is responsible for ligand binding and C-terminus confers resistance to enzymatic degradation[1][3][8]. Pharmacological modulation of the motilin receptor provides a means to manage gastrointestinal motility disorders such as **gastroparesis** and **IBS**, but challenges in drug development, safety, and receptor signaling remain[1][7][8]. The motilin receptor is homologous to the ghrelin receptor, but selectivity for motilin versus ghrelin is dictated by differences in ligand-binding pocket hydrophobicity and steric effects[7][8].

Other names

Motilin receptor (MTLR)MLN-RGPR38GPCR38Motilin receptor protein

Agonists induce contraction of gastric and intestinal smooth muscle via activation of motilin receptor and subsequent Gq protein-coupled intracellular signaling. Erythromycin and other macrolides function as motilin receptor agonists, mimicking motilin to enhance GI motility. Modulation of phase III of the migrating motor complex (MMC).