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.

The motilin receptor agonist erythromycin stimulates hunger and food intake through a cholinergic pathway

“…Furthermore, in contrast to rats and mice, it also expresses motilin (39). However, in the same species it has been shown that motilin induces phase III contractions independently of the vagus nerve via a myenteric cholinergic neural pathway (40,41). It is unclear whether the administration of a low dose of erythromycin is still able to induce a phase III contraction in vagotomized patients.…”

Motilin stimulates pepsinogen secretion in Suncus murinus

“…Recently, we found that motilin but not ghrelin stimulate gastric acid secretion in a dose dependent manner (manuscript preparation), and the intravenous administration of motilin causes gastric phase-III like contractions in suncus [22]. Gastric acid and pepsinogen secretion increase during the late phase II and phase III [23], and the higher luminal acid concentration leads to an increase in pepsinogen secretion in humans [24].…”

“…The body temperature of anesthetized suncus was monitored using a midi logger GL220 (Graphtec, Japan) and maintained at 35e38 C. In order to stabilize the amount of pepsinogen secreted, we allowed 60 min from the start of the saline perfusion before commencing effluent tube collection continuously at 10-min intervals using a DF-2000 fraction collector (Tokyo Rikakikai Co., Ltd., Tokyo, JAPAN). For experiments using vagotomized suncus, a truncal subdiaphragmatic vagotomy was performed as described previously [22]. In brief, the lower part of the esophagus was exposed to isolate the dorsal and ventral vagus nerves.…”

Therapeutic Applications of Ghrelin Agonists in the Treatment of Gastroparesis

“…The role of ghrelin on the migratory motor complex (MMC) has also been studied in several animal models to show stimulation of phase II of the MMC via the vagus nerve in the house musk shrew, Suncus murinus [52] and induction of a fasted motor pattern, enhancing motility of the antrum and duodenum in the fed or fasted state of healthy rodents [53][54][55][56].…”