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Motilin Stimulates Gastric Acid Secretion in Coordination with Ghrelin in Suncus murinus.

Goswami C, Shimada Y, Yoshimura M, Mondal A, Oda S, Tanaka T, Sakai T, Sakata I - PLoS ONE (2015)

Bottom Line: 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.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.Our results also suggest that motilin and co-administration of motilin and ghrelin stimulate gastric acid secretion via the histamine-mediated pathway in suncus.

View Article: PubMed Central - PubMed

Affiliation: Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama, Japan.

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.

No MeSH data available.


Related in: MedlinePlus

Effects of famotidine on motilin, and co-administration of motilin and ghrelin-stimulated gastric acid secretion.Gastric acid secretion was stimulated with histamine (1 mg/kg BW) (A, B), motilin (10 μg/kg BW) (D, E) and co-administration of motilin (10 μg/kg BW) and ghrelin (10 μg/kg BW) (G, H) with or without famotidine (0.33 mg/kg BW). In the left and middle panels, vehicle/famotidine was administrated intravenously 30 min before histamine (A, B), motilin (D, E) and co-administration of motilin and ghrelin (G, H). Gastric acid secretion (blue line) and pH (red line) changes were monitored at 10-min intervals throughout the experiment. Right panels represent the net change in cumulative acid output for 50 min after administration of histamine (C), motilin (F) and co-administration of motilin and ghrelin (I) with pre-administration of vehicle or famotidine. Each value represents the mean ± SEM. p < 0.05 was considered statistically significant. F: famotidine; G: ghrelin; M: motilin, figures after the abbreviations denote concentration in μg/kg. n = 3–4.
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pone.0131554.g002: Effects of famotidine on motilin, and co-administration of motilin and ghrelin-stimulated gastric acid secretion.Gastric acid secretion was stimulated with histamine (1 mg/kg BW) (A, B), motilin (10 μg/kg BW) (D, E) and co-administration of motilin (10 μg/kg BW) and ghrelin (10 μg/kg BW) (G, H) with or without famotidine (0.33 mg/kg BW). In the left and middle panels, vehicle/famotidine was administrated intravenously 30 min before histamine (A, B), motilin (D, E) and co-administration of motilin and ghrelin (G, H). Gastric acid secretion (blue line) and pH (red line) changes were monitored at 10-min intervals throughout the experiment. Right panels represent the net change in cumulative acid output for 50 min after administration of histamine (C), motilin (F) and co-administration of motilin and ghrelin (I) with pre-administration of vehicle or famotidine. Each value represents the mean ± SEM. p < 0.05 was considered statistically significant. F: famotidine; G: ghrelin; M: motilin, figures after the abbreviations denote concentration in μg/kg. n = 3–4.

Mentions: We next examined the effect of famotidine (an H2 receptor antagonist) on motilin, and co-administration of motilin and ghrelin-stimulated gastric acid secretion. Famotidine (0.33 mg/kg) significantly decreased histamine-induced acid output and also inhibited the decrease in pH by histamine treatment (Fig 2A–2C). In order to examine whether the H2 receptor is the mediator of motilin and combined motilin and ghrelin-stimulated acid secretion, i.v. administration of vehicle and famotidine (0.33 mg/kg) was done 30 min before the administration of motilin (10 μg/kg) and co-administration of motilin (10 μg/kg) and ghrelin (10 μg/kg). Famotidine treatment gradually decreased baseline acid secretion; however, no peak was observed after motilin administration. The stimulatory effect of motilin on gastric acid secretion was completely inhibited by famotidine treatment (Fig 2D–2F). Similarly, the effect of co-administration of motilin and ghrelin was almost completely eliminated by famotidine treatment (Fig 2G–2I).


Motilin Stimulates Gastric Acid Secretion in Coordination with Ghrelin in Suncus murinus.

Goswami C, Shimada Y, Yoshimura M, Mondal A, Oda S, Tanaka T, Sakai T, Sakata I - PLoS ONE (2015)

Effects of famotidine on motilin, and co-administration of motilin and ghrelin-stimulated gastric acid secretion.Gastric acid secretion was stimulated with histamine (1 mg/kg BW) (A, B), motilin (10 μg/kg BW) (D, E) and co-administration of motilin (10 μg/kg BW) and ghrelin (10 μg/kg BW) (G, H) with or without famotidine (0.33 mg/kg BW). In the left and middle panels, vehicle/famotidine was administrated intravenously 30 min before histamine (A, B), motilin (D, E) and co-administration of motilin and ghrelin (G, H). Gastric acid secretion (blue line) and pH (red line) changes were monitored at 10-min intervals throughout the experiment. Right panels represent the net change in cumulative acid output for 50 min after administration of histamine (C), motilin (F) and co-administration of motilin and ghrelin (I) with pre-administration of vehicle or famotidine. Each value represents the mean ± SEM. p < 0.05 was considered statistically significant. F: famotidine; G: ghrelin; M: motilin, figures after the abbreviations denote concentration in μg/kg. n = 3–4.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4482737&req=5

pone.0131554.g002: Effects of famotidine on motilin, and co-administration of motilin and ghrelin-stimulated gastric acid secretion.Gastric acid secretion was stimulated with histamine (1 mg/kg BW) (A, B), motilin (10 μg/kg BW) (D, E) and co-administration of motilin (10 μg/kg BW) and ghrelin (10 μg/kg BW) (G, H) with or without famotidine (0.33 mg/kg BW). In the left and middle panels, vehicle/famotidine was administrated intravenously 30 min before histamine (A, B), motilin (D, E) and co-administration of motilin and ghrelin (G, H). Gastric acid secretion (blue line) and pH (red line) changes were monitored at 10-min intervals throughout the experiment. Right panels represent the net change in cumulative acid output for 50 min after administration of histamine (C), motilin (F) and co-administration of motilin and ghrelin (I) with pre-administration of vehicle or famotidine. Each value represents the mean ± SEM. p < 0.05 was considered statistically significant. F: famotidine; G: ghrelin; M: motilin, figures after the abbreviations denote concentration in μg/kg. n = 3–4.
Mentions: We next examined the effect of famotidine (an H2 receptor antagonist) on motilin, and co-administration of motilin and ghrelin-stimulated gastric acid secretion. Famotidine (0.33 mg/kg) significantly decreased histamine-induced acid output and also inhibited the decrease in pH by histamine treatment (Fig 2A–2C). In order to examine whether the H2 receptor is the mediator of motilin and combined motilin and ghrelin-stimulated acid secretion, i.v. administration of vehicle and famotidine (0.33 mg/kg) was done 30 min before the administration of motilin (10 μg/kg) and co-administration of motilin (10 μg/kg) and ghrelin (10 μg/kg). Famotidine treatment gradually decreased baseline acid secretion; however, no peak was observed after motilin administration. The stimulatory effect of motilin on gastric acid secretion was completely inhibited by famotidine treatment (Fig 2D–2F). Similarly, the effect of co-administration of motilin and ghrelin was almost completely eliminated by famotidine treatment (Fig 2G–2I).

Bottom Line: 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.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.Our results also suggest that motilin and co-administration of motilin and ghrelin stimulate gastric acid secretion via the histamine-mediated pathway in suncus.

View Article: PubMed Central - PubMed

Affiliation: Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama, Japan.

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.

No MeSH data available.


Related in: MedlinePlus