The upper gastrointestinal (GI) tract undergoes a temporally coordinated cyclic motor pattern known as the migrating motor complex (MMC) in both dogs and humans during the fasted state. Feeding results in replacement of the MMC by a pattern of noncyclic, intermittent contractile activity termed as postprandial contractions. Although the MMC is known to be stimulated by motilin, recent studies have shown that ghrelin, which is from the same peptide family as motilin, is also involved in the regulation of the MMC. In the present study, we investigated the role of the vagus nerve on gastric motility using conscious suncus—a motilin- and ghrelin-producing small animal. During the fasted state, cyclic MMC comprising phases I, II, and III was observed in both sham-operated and vagotomized suncus; however, the duration and motility index (MI) of phase II was significantly decreased in vagotomized animals. Motilin infusion (50 ng·kg−1·min−1 for 10 min) during phase I had induced phase III–like contractions in both sham-operated and vagotomized animals. Ghrelin infusion (0.1, 0.3, 1, 3, or 10 µg·kg−1·min−1 for 10 min) enhanced the amplitude of phase II MMC in sham-operated animals, but not in vagotomized animals. After feeding, phase I was replaced by postprandial contractions, and motilin infusion (50 ng·kg−1·min−1 for 10 min) did not induce phase III–like contractions in sham-operated suncus. However, in vagotomized suncus, feeding did not evoke postprandial contractions, but exogenous motilin injection strongly induced phase III–like contractions, as noted during the phase I period. Thus, the results indicate that ghrelin stimulates phase II of the MMC via the vagus nerve in suncus. Furthermore, the vagus nerve is essential for initiating postprandial contractions, and inhibition of the phase III–like contractions induced by motilin is highly dependent on the vagus nerve.

Motilin was discovered in the 1970s as the most important hormone for stimulating strong gastric contractions; however, the mechanisms by which motilin causes gastric contraction are not clearly understood. Here, we determined the coordinated action of motilin and ghrelin on gastric motility during fasted and postprandial contractions by using house musk shrew (Suncus murinus; order: Insectivora, suncus named as the laboratory strain). Motilin-induced gastric contractions at phases I and II of the migrating motor complex were inhibited by pretreatment with (D-Lys(3))-GHRP-6 (6 mg/kg/h), a ghrelin receptor antagonist. Administration of the motilin receptor antagonist MA-2029 (0.1 mg/kg) and/or (D-Lys(3))-GHRP-6 (0.6 mg/kg) at the peak of phase III abolished the spontaneous gastric phase III contractions in vivo. Motilin did not stimulate gastric contractions in the postprandial state. However, in the presence of a low dose of ghrelin, motilin evoked phase III-like gastric contractions even in the postprandial state, and postprandial gastric emptying was accelerated. In addition, pretreatment with (D-Lys(3))-GHRP-6 blocked the motilin-induced gastric contraction in vitro and in vivo, and a γ-aminobutyric acid (GABA) antagonist reversed this block in gastric contraction. These results indicate that blockade of the GABAergic pathway by ghrelin is essential for motilin-induced gastric contraction.

Gastric acidification in S. murinus inhibits motilin-induced contractions, a finding similar to results observed in humans, while TRPV1-expressing vagus nerves play a role in the inhibitory mechanism.

Ghrelin, a peptide hormone produced in the stomach, has been known to be involved in the regulation of gastric contraction in humans and rodents. To elucidate the detailed mechanisms of ghrelin on gastric contractions, we used Suncus murinus, a recently established small animal model for gastrointestinal motility. S. murinus produces motilin, a family peptide of ghrelin, and its stomach anatomy and physiological patterns of gastric contractions, in fed and fasted states, are closely similar to humans. Ghrelin administration in phase II, and latter half of phase I, of the migrating motor contractions (MMC) enhanced gastric motility in S. murinus. In addition, we showed that ghrelin and motilin coordinately stimulated strong gastric contractions in vitro and in vivo. We also demonstrated that a pretreatment with a ghrelin antagonist, D-Lys3-GHRP6, inhibited the effects of motilin-induced gastric contractions, and a γ-aminobutyric acid (GABA) antagonist reversed this inhibition. Our results suggest that ghrelin is essential for motilin-induced gastric contractions and that ghrelin-mediated GABAergic neurons are involved in this neural pathway.