Effects of Motilin Receptor Agonists and Ghrelin in Human motilin receptor Transgenic Mice

• Published in: International journal of molecular sciences Vol. 20; no. 7; p. 1521
• Main Authors: Kawamura, Tomoe, Matsuura, Bunzo, Miyake, Teruki, Abe, Masanori, Ikeda, Yoshiou, Hiasa, Yoichi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.03.2019; MDPI
• Subjects: Antibiotics; Drug dosages; erythromycin; gastric emptying; Ghrelin; motilin; Motility; Peptides; Stomach; Transgenic animals; Transgenic mice; ghrelin; gastric emptying; erythromycin; motilin
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20071521

Gastrointestinal motility is regulated by neural factors and humoral factors. Both motilin and ghrelin improve gastrointestinal motility, but many issues remain unclear. We prepared human transgenic (Tg) mice and performed experiments evaluating the effects of motilin, erythromycin (EM), and ghrelin. EM and ghrelin promoted gastric emptying (GE) when administered either peripherally or centrally to Tg mice. Atropine (a muscarinic receptor antagonist) counteracted GE induced by centrally administered EM, but not that induced by peripherally administered EM. The administration of EM in this model promoted the effect of mosapride (a selective serotonin 5-hydroxytryptamine 4 (5-HT4) receptor agonist), and improved loperamide (a μ-opioid receptor agonist)-induced gastroparesis. The level of acyl-ghrelin was significantly attenuated by EM administration. Thus, we have established an animal model appropriate for the evaluation of motilin receptor agonists. These data and the model are expected to facilitate the identification of novel compounds with clinical potential for relieving symptoms of dyspepsia and gastroparesis.