The role of the vagus nerve in the migrating motor complex and ghrelin- and motilin-induced gastric contraction in suncus

Abstract

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.

Figure 1. Spontaneous gastric contractions in sham-operated and vagotomized, fasted suncus.

(A) Regular, cyclic, spontaneous MMC with phase I, II, and III contractions was observed in the stomach of sham-operated suncus. (B) In vagotomized suncus, the amplitude of phase II contractions was decreased, although spontaneous MMC was also observed. Asterisks indicate the phase III contraction. (C) The entire period of the MMC and the duration of phase III were unchanged between sham and vagotomized suncus; however, the duration of phase I was increased in vagotomized suncus. In contrast, the duration of phase II was significantly shorter in vagotomized suncus than in sham-operated animals. (D) The motility index of phase II was significantly lower in vagotomized suncus than in sham-operated suncus. * Phase III contractions. #, p<0.05; ##, p<0.01; n = 5.

Figure 2. The effect of ghrelin administration on phase II of the MMC.

Ghrelin (0.1, 0.3, 1, 3, or 10 µg·kg⁻¹·min⁻¹ for 10 min) was intravenously administered during phase II of the MMC (10 min after the initiation of phase II) in sham-operated (A) and vagotomized (B) suncus. Ghrelin administration was found to enhance the phase II contraction in sham-operated suncus but not vagotomized suncus. (C) The motility index was statistically increased in sham-operated suncus compared with vagotomized suncus. * Phase III contractions. #, p<0.05; ##, p<0.01; n = 4.

Figure 3. The effect of motilin administration on phase I of the MMC.

Motilin (50 ng·kg⁻¹·min⁻¹ for 10 min) was intravenously administered during phase I of the MMC (10 min after the end of phase III) in sham-operated (A) and vagotomized (B) suncus. The motility index (C) and duration (D) of motilin administration was not differentially affected between the stomachs of sham-operated and vagotomized suncus. * Phase III contractions. Sham, n = 8; vagotomy, n = 5.

Figure 4. The effect of motilin administration in the postprandial state.

Motilin (50 ng·kg⁻¹·min⁻¹ for 10 min) was intravenously administered in the postprandial state (20 min after the initiation of feeding) in sham (A) and vagotomized (B) suncus. Motilin did not induce contraction in the stomachs of sham-operated animals (A); however, motilin induced strong contractions in the stomachs of vagotomized suncus (B). The motility index for 10 min from feeding was significantly decreased in vagotomized suncus (C). However, the motility index during motilin administration increased in vagotomized suncus (D). * Phase III contractions. #, p<0.05; ##, p<0.01; sham, n = 5; vagotomy, n = 3.

Figure 5. Working hypothesis of the regulatory mechanisms of the MMC and postprandial contractions in suncus.

During the fasted state, endogenous ghrelin secreted from X/A cells acts on the brain and stimulates and maintains gastric phase II of the MMC through vagal efferent nerves. Ghrelin also directly acts on the stomach through the circulation, and initiates gastric phase III contractions in coordination with motilin secreted from M cells (A). Postprandial contractions are initiated and maintained by the vagus nerve, and motilin-induced contractions are inhibited by a vagus nerve–related pathway (B).