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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 motilin and ghrelin on gastric acid secretion.In urethane-anaesthetized suncus, after a 60-min basal period, gastric acid secretion was measured after administration of histamine (1 mg/kg BW) (A), vehicle (B), ghrelin (0.1, 1.0, and 10 μg/kg BW) (C), motilin (0.1, 1.0, and 10 μg/kg BW) (D), and co-administration of motilin and ghrelin (E). Gastric acid secretion (blue line) and pH (red line) changes were monitored at 10-min intervals throughout the experiment. The net change in cumulative acid output for 50 min after each administration was also calculated (F). Each value represents the mean ± SEM. p < 0.05 was considered statistically significant. G: ghrelin; M: motilin, figures after the abbreviations denote concentration in μg/kg. n = 3–7.
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pone.0131554.g001: Effects of motilin and ghrelin on gastric acid secretion.In urethane-anaesthetized suncus, after a 60-min basal period, gastric acid secretion was measured after administration of histamine (1 mg/kg BW) (A), vehicle (B), ghrelin (0.1, 1.0, and 10 μg/kg BW) (C), motilin (0.1, 1.0, and 10 μg/kg BW) (D), and co-administration of motilin and ghrelin (E). Gastric acid secretion (blue line) and pH (red line) changes were monitored at 10-min intervals throughout the experiment. The net change in cumulative acid output for 50 min after each administration was also calculated (F). Each value represents the mean ± SEM. p < 0.05 was considered statistically significant. G: ghrelin; M: motilin, figures after the abbreviations denote concentration in μg/kg. n = 3–7.

Mentions: To establish the perfusion system for gastric acid experiment in suncus, we first examined the effect of histamine (1 mg/kg) on acid secretion (Fig 1A). Intravenous (i.v.) administration of histamine started to increase the acid output after 10 min and reached its maximum at 20 min, after which the acid output reduced to baseline around 30–40 min after histamine administration (Fig 1A). The pH of the gastric output had maximally decreased 20 min after histamine administration and restored to its previous values at 40 min after administration (Fig 1A). The amount of acid secretion induced by 1 mg/kg histamine was 4.22 ± 0.32 μEq/50 min and the acid output significantly increased compared to the vehicle (control: 0.52 ± 0.27 μEq/50 min) (Fig 1F). Vehicle administration (0.1% BSA in PBS) did not change the basal gastric acid secretion (Fig 1B). The i.v. administration of ghrelin at the doses of 0.1, 1.0, and 10 μg/kg did not increase the acid output and the pH was slightly decreased, but not significantly so (Fig 1C). In contrast, i.v. administration of motilin started to increase acid secretion after 10 min and reached its maximum at 20 min after administration (Fig 1D). The motilin-induced acid secretion returned to baseline 40 min after administration and the pH value of the gastric output decreased within 30–40 min of motilin administration (Fig 1D). The amount of gastric acid secretion 50 min after motilin administration at the doses of 0.1, 1.0, and 10 μg/kg increased dose-dependently (Fig 1F). Co-administration of motilin and ghrelin (0.1, 1.0, and 10 μg/kg BW each) also induced the secretion of gastric acid and it reached its maximum in 20 min after administration, and decayed gradually before 50 min had elapsed (Fig 1E). A maximum decline of gastric pH was observed within 20 min and returned to baseline 50 min after the administration of each dose (Fig 1E). The amount of gastric acid secretion 50 min after co-administration of motilin and ghrelin increased in a dose-dependent manner (Fig 1F). Statistical analysis showed that 10 μg/kg motilin, and co-administration of motilin and ghrelin (1 and 10 μg/kg, each) significantly increased acid output compared to vehicle administration (Fig 1F).


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 motilin and ghrelin on gastric acid secretion.In urethane-anaesthetized suncus, after a 60-min basal period, gastric acid secretion was measured after administration of histamine (1 mg/kg BW) (A), vehicle (B), ghrelin (0.1, 1.0, and 10 μg/kg BW) (C), motilin (0.1, 1.0, and 10 μg/kg BW) (D), and co-administration of motilin and ghrelin (E). Gastric acid secretion (blue line) and pH (red line) changes were monitored at 10-min intervals throughout the experiment. The net change in cumulative acid output for 50 min after each administration was also calculated (F). Each value represents the mean ± SEM. p < 0.05 was considered statistically significant. G: ghrelin; M: motilin, figures after the abbreviations denote concentration in μg/kg. n = 3–7.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4482737&req=5

pone.0131554.g001: Effects of motilin and ghrelin on gastric acid secretion.In urethane-anaesthetized suncus, after a 60-min basal period, gastric acid secretion was measured after administration of histamine (1 mg/kg BW) (A), vehicle (B), ghrelin (0.1, 1.0, and 10 μg/kg BW) (C), motilin (0.1, 1.0, and 10 μg/kg BW) (D), and co-administration of motilin and ghrelin (E). Gastric acid secretion (blue line) and pH (red line) changes were monitored at 10-min intervals throughout the experiment. The net change in cumulative acid output for 50 min after each administration was also calculated (F). Each value represents the mean ± SEM. p < 0.05 was considered statistically significant. G: ghrelin; M: motilin, figures after the abbreviations denote concentration in μg/kg. n = 3–7.
Mentions: To establish the perfusion system for gastric acid experiment in suncus, we first examined the effect of histamine (1 mg/kg) on acid secretion (Fig 1A). Intravenous (i.v.) administration of histamine started to increase the acid output after 10 min and reached its maximum at 20 min, after which the acid output reduced to baseline around 30–40 min after histamine administration (Fig 1A). The pH of the gastric output had maximally decreased 20 min after histamine administration and restored to its previous values at 40 min after administration (Fig 1A). The amount of acid secretion induced by 1 mg/kg histamine was 4.22 ± 0.32 μEq/50 min and the acid output significantly increased compared to the vehicle (control: 0.52 ± 0.27 μEq/50 min) (Fig 1F). Vehicle administration (0.1% BSA in PBS) did not change the basal gastric acid secretion (Fig 1B). The i.v. administration of ghrelin at the doses of 0.1, 1.0, and 10 μg/kg did not increase the acid output and the pH was slightly decreased, but not significantly so (Fig 1C). In contrast, i.v. administration of motilin started to increase acid secretion after 10 min and reached its maximum at 20 min after administration (Fig 1D). The motilin-induced acid secretion returned to baseline 40 min after administration and the pH value of the gastric output decreased within 30–40 min of motilin administration (Fig 1D). The amount of gastric acid secretion 50 min after motilin administration at the doses of 0.1, 1.0, and 10 μg/kg increased dose-dependently (Fig 1F). Co-administration of motilin and ghrelin (0.1, 1.0, and 10 μg/kg BW each) also induced the secretion of gastric acid and it reached its maximum in 20 min after administration, and decayed gradually before 50 min had elapsed (Fig 1E). A maximum decline of gastric pH was observed within 20 min and returned to baseline 50 min after the administration of each dose (Fig 1E). The amount of gastric acid secretion 50 min after co-administration of motilin and ghrelin increased in a dose-dependent manner (Fig 1F). Statistical analysis showed that 10 μg/kg motilin, and co-administration of motilin and ghrelin (1 and 10 μg/kg, each) significantly increased acid output compared to vehicle administration (Fig 1F).

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