Motilin Receptor Antibodies

The motilin receptor (MLNR, also known as GPR38 or MTLR1) is a class A G protein-coupled receptor (GPCR) that is activated by the gastrointestinal peptide hormone motilin and primarily couples to Gq/11 proteins, leading to phospholipase C activation, intracellular calcium mobilization, and smooth muscle contraction. It is predominantly expressed in the smooth muscle and enteric neurons of the upper gastrointestinal tract, particularly in the stomach and duodenum, where it regulates the migrating motor complex during fasting. Lower levels of expression have also been reported in the thyroid and bone marrow. Activation of MLNR stimulates gastric emptying, enhances gastrointestinal motility, and coordinates interdigestive peristaltic activity. Besides endogenous motilin, several macrolide antibiotics, most notably erythromycin, act as non-peptide motilin receptor agonists and exhibit potent prokinetic effects. These compounds have been used off-label for the treatment of gastroparesis and other gastrointestinal hypomotility disorders, although long-term use is limited by tachyphylaxis and antibiotic-related adverse effects. More selective, non-antibiotic motilin receptor agonists, including camicinal (GSK962040) and mitemcinal (GM-611), have been developed and evaluated in clinical trials to improve gastric motility. Although none of these newer agonists has yet achieved widespread clinical approval, the motilin receptor remains an attractive therapeutic target for disorders characterized by delayed gastric emptying and impaired upper gastrointestinal motility. For more information on motilin receptor pharmacology please refer to the IUPHAR database.