Goswami Chayon, Shimada Yoshiaki, Yoshimura Makoto, Mondal Anupom, Oda Sen-ichi, Tanaka Toru, Sakai Takafumi, Sakata Ichiro
Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama, Japan.
Laboratory of Animal Management and Resources, Department of Zoology, Okayama University of Science, Okayama, Japan.
PLoS One. 2015 Jun 26;10(6):e0131554. doi: 10.1371/journal.pone.0131554. eCollection 2015.
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.
胃动素和胃饥饿素构成一个肽家族，这些激素对胃肠动力的调节很重要。在本研究中，我们检测了胃动素和胃饥饿素对麻醉的臭鼩（家麝鼩，Suncus murinus）胃酸分泌的影响，臭鼩是一种能产生胃饥饿素和胃动素的哺乳动物。我们首先在臭鼩中建立了胃腔灌注系统，并证实静脉注射组胺（1毫克/千克体重）可刺激胃酸分泌。胃动素（0.1、1.0和10微克/千克体重）在臭鼩中以剂量依赖的方式刺激胃酸分泌，而单独使用胃饥饿素（0.1、1.0和10微克/千克体重）不会诱导胃酸分泌。此外，与给予赋形剂相比，低剂量（1微克/千克体重）胃动素和胃饥饿素共同给药显著刺激胃酸分泌，而单独使用胃动素（1微克/千克体重）或胃饥饿素（1微克/千克体重）均未显著诱导胃酸分泌。这表明胃饥饿素在胃动素诱导的胃酸分泌中具有累加作用。然后，我们使用受体拮抗剂研究了胃动素/胃动素和胃饥饿素刺激胃酸分泌的途径。用YM 022（一种CCK - B受体拮抗剂）和阿托品（一种毒蕈碱型乙酰胆碱受体拮抗剂）处理对胃动素或胃动素 - 胃饥饿素共同给药诱导的胃酸分泌没有影响。相比之下，法莫替丁（一种组胺H2受体拮抗剂）完全抑制胃动素刺激的胃酸分泌，胃动素和胃饥饿素共同给药可诱导胃酸分泌。这是首次证明胃动素刺激哺乳动物胃酸分泌的报告。我们的结果还表明，胃动素以及胃动素和胃饥饿素共同给药通过组胺介导的途径刺激臭鼩胃酸分泌。
