Motilin receptor (MLNR) (MLNR)

The motilin receptor (MLNR) is a Class A G protein-coupled receptor that serves as the primary mediator of the motilin-induced gastrointestinal motility pathway [1][2]. It is predominantly localized in the smooth muscle cells and enteric nerves of the human stomach and duodenum, where it responds to the 22-amino acid peptide motilin secreted by enteroendocrine M cells [1][3]. Activation of this receptor is essential for initiating Phase III of the migrating motor complex (MMC), a series of strong peristaltic contractions that clear the stomach and small intestine of undigested material during the fasting state [3]. Because of its potent prokinetic effects, the motilin receptor is a significant therapeutic target for disorders characterized by delayed gastric emptying, such as diabetic and idiopathic gastroparesis [4]. Pharmacological intervention has historically relied on macrolide antibiotics like erythromycin, which act as motilin agonists, though modern drug development focuses on non-antibiotic motilides to mitigate the risk of bacterial resistance [5]. Despite their efficacy, many motilin receptor agonists face challenges such as tachyphylaxis, where the receptor undergoes rapid desensitization, and potential cardiovascular side effects like QT prolongation [2][4].

Other names

G-protein coupled receptor 38GPR38MTLR1MOTRMotilin receptor 1Motilin receptor

Agonists bind to the motilin receptor, activating the Gq/11 signaling pathway, which stimulates phospholipase C and increases intracellular calcium levels, leading to smooth muscle contraction in the gastrointestinal tract.