Growth hormone secretagogue receptor (GHSR) and Motilin receptor (MLNR) (GHSR/MLNR)

The neuroendocrine regulation of the gut-brain axis via ghrelin and motilin involves two highly homologous G protein-coupled receptors: the growth hormone secretagogue receptor (GHSR) and the motilin receptor (MLNR) [PMID: 28262254]. Ghrelin, primarily secreted by the stomach, acts on GHSR in the central nervous system to stimulate food intake and the release of growth hormone from the pituitary gland [PMID: 8700204]. Motilin, secreted by the duodenum, acts on MLNR to trigger the migrating motor complex, which is essential for clearing the stomach and small intestine of undigested material during fasting [PMID: 10444062]. These pathways are critical for maintaining energy balance and gastrointestinal motility. Pharmacological targeting of these receptors includes GHSR agonists like anamorelin for treating cancer-associated cachexia and MLNR agonists like relamorelin or erythromycin derivatives for gastroparesis [PMID: 26900150, PMID: 27107700]. However, therapeutic challenges include the rapid desensitization of the motilin receptor and potential metabolic side effects associated with chronic ghrelin receptor activation.

Other names

Ghrelin receptorGHS-RGHS-R1aMotilin receptorMLNRGPR38MTLR1Ghrelin/Motilin receptor family

Agonism of the growth hormone secretagogue receptor (GHSR) to stimulate appetite and growth hormone release; Agonism of the motilin receptor (MLNR) to induce phase III of the migrating motor complex and accelerate gastric emptying.