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Endocrine Abstracts (2020) 70 AEP728 | DOI: 10.1530/endoabs.70.AEP728

1Ehime University Graduate School of Medicine, Lifestyle-related Medicine & Endocrinology, Toon, Japan; 2Ehime University Graduate School of Medicine, Gastroenterology & Metabology, Toon, Japan


Motilin (M), erythromycin (EM) and ghrelin (G) are recognized as important regulators of gastrointestinal motor function in humans that are mediated by class I guanine nucleotide-binding protein (G protein)-coupled motilin receptor (MR) and growth hormone secretagogue receptor (GHSR). These receptors have also been demonstrated as clinically useful pharmacological targets. However, a molecular relationship between MR and GHSR activation has been unclear. We generated human MR transgenic (hMR-Tg) mice because rodents do not endogenously express M and MR. In the current study, we examined gastric prokinetic effects, and relationship between M and G after administration of M, EM and G in hMR-Tg mice. M and EM affected concentration-dependent contraction of gastric smooth muscle in hMR-Tg mice but not in WT mice. Intraperitoneal (ip) and intracerebroventricular (icv) administration of EM significantly promoted gastric emptying in hMR-Tg mice but not in WT mice. The changes in gastric empty responses to EM icv administration were altered by atropin, but those to EM ip administration was not. G ip and icv administration significantly promoted gastric emptying in both hMR-Tg mice and WT mice. EM ip and icv administration reduced serum ghrelin concentration. According to our data, the hMR-Tg mice are useful for the evaluation of gastric prokinetic drugs in humans.

Volume 70

22nd European Congress of Endocrinology

Online
05 Sep 2020 - 09 Sep 2020

European Society of Endocrinology 

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