Abstract
Motilin and ghrelin constitute a peptide family, and these hormones are important for the regulation of gastrointestinal motility. In this study, we examined the effect of motilin and ghrelin on gastric acid secretion in anesthetized suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin-producing mammal. We first established a gastric lumen-perfusion system in the suncus and confirmed that intravenous (i.v.) administration of histamine (1 mg/kg body weight) stimulated acid secretion. Motilin (0.1, 1.0, and 10 μg/kg BW) stimulated the acid output in a dose-dependent manner in suncus, whereas ghrelin (0.1, 1.0, and 10 μg/kg BW) alone did not induce acid output. Furthermore, in comparison with the vehicle administration, the co-administration of low-dose (1 μg/kg BW) motilin and ghrelin significantly stimulated gastric acid secretion, whereas either motilin (1 μg/kg BW) or ghrelin (1 μg/kg BW) alone did not significantly induce gastric acid secretion. This indicates an additive role of ghrelin in motilin-induced gastric acid secretion. We then investigated the pathways of motilin/motilin and ghrelin-stimulated acid secretion using receptor antagonists. Treatment with YM 022 (a CCK-B receptor antagonist) and atropine (a muscarinic acetylcholine receptor antagonist) had no effect on motilin or motilin-ghrelin co-administration-induced acid output. In contrast, famotidine (a histamine H2 receptor antagonist) completely inhibited motilin-stimulated acid secretion and co-administration of motilin and ghrelin induced gastric acid output. This is the first report demonstrating that motilin stimulates gastric secretion in mammals. Our results also suggest that motilin and co-administration of motilin and ghrelin stimulate gastric acid secretion via the histamine-mediated pathway in suncus.
Highlights
It is well established that gastric acid secretion is regulated by neurocrine, endocrine, and paracrine signals [1]
We reported that motilin and ghrelin synergistically stimulated gastric contraction in suncus, suggesting that focusing on the coordination of motilin and ghrelin is important for understanding their physiological role [25]
We used suncus as a model animal to study the effect of motilin and/or ghrelin on gastric acid secretion
Summary
It is well established that gastric acid secretion is regulated by neurocrine, endocrine, and paracrine signals [1]. It is well known that ghrelin is a multifunctional hormone; many studies revealed that ghrelin is important for the regulation of gastrointestinal tract [4, 6, 10,11,12,13,14], in particular, it stimulates gastric acid secretion in the rat [15], and induces gastric motility by peripheral or central administration [16, 17]. Complete cDNA sequences and the tissue distribution of motilin and ghrelin were identified in suncus [30, 31] These results suggest that suncus is a useful animal for studying gastrointestinal physiology, including gastric motility. We examined the acid secretion mechanism by motilin and co-administration of motilin and ghrelin, using receptor antagonists
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