Coordination of motilin and ghrelin regulates the migrating motor complex of gastrointestinal motility in Suncus murinus

Abstract

Motilin and ghrelin are the gastrointestinal (GI) hormones released in a fasting state to stimulate the GI motility of the migrating motor complex (MMC). We focused on coordination of the ghrelin/motilin family in gastric contraction in vivo and in vitro using the house musk shrew (Suncus murinus), a ghrelin- and motilin-producing mammal. To measure the contractile activity of the stomach in vivo, we recorded GI contractions either in the free-moving conscious or anesthetized S. murinus and examined the effects of administration of motilin and/or ghrelin on spontaneous MMC in the fasting state. In the in vitro study, we also studied the coordinative effect of these hormones on the isolated stomach using an organ bath. In the fasting state, phase I, II, and III contractions were clearly recorded in the gastric body (as observed in humans and dogs). Intravenous infusion of ghrelin stimulated gastric contraction in the latter half of phase I and in the phase II in a dose-dependent manner. Continuous intravenous infusion of ghrelin antagonist (d-Lys3-GHRP6) significantly suppressed spontaneous phase II contractions and prolonged the time of occurrence of the peak of phase III contractions. However, intravenous infusion of motilin antagonist (MA-2029) did not inhibit phase II contractions but delayed the occurrence of phase III contractions of the MMC. In the in vitro study, even though a high dose of ghrelin did not stimulate contraction of stomach preparations, ghrelin administration (10(-10)-10(-7) M) with pretreatment of a low dose of motilin (10(-10) M) induced gastric contraction in a dose-dependent manner. Pretreatment with 10(-8) M ghrelin enhanced motilin-stimulated gastric contractions by 10 times. The interrelation of these peptides was also demonstrated in the anesthetized S. murinus. The results suggest that ghrelin is important for the phase II contraction and that coordination of motilin and ghrelin are necessary to initiate phase III contraction of the MMC.

The proximal gastric corpus is the most responsive site of motilin-induced contractions in the stomach of the Asian house shrew

“…Different letters denote significant difference (P < 0.05) among groups the proximal corpus is the first site in which contractions are induced by motilin stimulation. Our previous in vivo study showed that ghrelin was important for the initiation of phase III MMC contractions and that co-administration of motilin and ghrelin-induced a synergistic phasic response in the prepared isolated stomachs at concentrations ranging from 10 −9 to 10 −7 M in a dose-dependent manner (Mondal et al 2012). Therefore, it would be interesting to conduct further research on the response to motilin and ghrelin co-administration in different parts of the stomach.…”

“…Tissues with mucosa attached to the muscle layer were used instead of muscle layer strips. The longitudinal and circular muscle layers were not been separated into strips because as previously shown, myenteric plexus is important for motilininduced Suncus gastric contractions (Mondal et al 2012), and keeping an intact anatomical structure of the myenteric neuron and smooth muscle is essential for studying motilin-induced contraction. The segmented stomach parts were mounted in 10-mL water-jacketed organ baths along the longitudinal muscle direction with the thread tied on cut edge surfaces.…”

Rikkunshito, a Kampo Medicine, Ameliorates Post-operative Ileus by Anti-inflammatory Action

“…1. HPLC analysis revealed that the prepared RKT contained important active ingredients such as liquiritin, hesperidin, ginsenoside Rg1, glycyrrhizin, [6]-gingerol and [6]-shogaol.…”

G protein-coupled receptor 120 signaling regulates ghrelin secretion in vivo and in vitro

“…Ghrelin was first shown to stimulate growth hormone release from the anterior pituitary gland in vivo and in vitro (15,33) and was later found to be deeply involved in the regulation of feeding behavior and energy homeostasis (20,27,30,32). In addition to these physiological functions, ghrelin has been shown to play several roles in the stimulation of gastric motility, cell proliferation, mood, and torpor (1,3,6,10,14,19). The binding of ghrelin to its specific receptor, GHS-R, and its biological activity are entirely dependent on the attachment of octanoate to the third serine residue, a reaction catalyzed by ghrelin O-acyltransferase (GOAT) (34).…”