Myenteric neural network activated by motilin in the stomach of Suncus murinus (house musk shrew)

Mondal, Anupom; Kawamoto, Yoichi; Yanaka, Takatsugu; Tsutsui, Chihiro; Sakata, Ichiro; Oda, Sen-ichi; Tanaka, Toru; Sakai, Takafumi

doi:10.1111/j.1365-2982.2011.01801.x

Cited by 27 publications

(34 citation statements)

References 51 publications

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“…From in vivo and in vitro experiments using S. murinus, we demonstrated that motilin-induced gastric contractions are mediated through the myenteric plexus (Mondal et al 2011;Sakahara et al 2010). Similar results have been reported in other species (De Smet et al 2009;Kitazawa et al 1995;Mizumoto et al 1993;Ohshiro et al 2008;Van Assche et al 1997).…”

Section: Introductionsupporting

confidence: 86%

“…The response to motilin in the proximal corpus was higher than that in the other parts of the stomach, especially with the low motilin concentration, i.e., the 10 −10 M motilin concentration, which slightly induced contractions and the contraction response at 10 −9 M were significantly higher in the proximal corpus than that in the other parts. We previously published reports of concentration-dependent contractile effects of motilin on the isolated S. murinus whole stomach in vitro, and there reported that motilin-induced contraction occurred starting from the 10 −9 M concentration (Mondal et al 2011). Even though the stomach was divided into four sections, each of sections retained the ability to react to motilin, similar to that observed in vitro in the whole stomach.…”

Section: Discussionmentioning

confidence: 55%

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

et al. 2016

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The migrating motor complex (MMC) is responsible for emptying the stomach during the interdigestive period, in preparation for the next meal. It is known that gastric phase III of MMC starts from the proximal stomach and propagates the contraction downwards. We hypothesized that a certain region of the stomach must be more responsive to motilin than others, and that motilin-induced strong gastric contractions propagate from that site. Stomachs of the Suncus or Asian house shrew, a small insectivorous mammal, were dissected and the fundus, proximal corpus, distal corpus, and antrum were examined to study the effect of motilin using an organ bath experiment. Motilin-induced contractions differed in different parts of the stomach. Only the proximal corpus induced gastric contraction even at motilin 10(-10) M, and strong contraction was induced by motilin 10(-9) M in all parts of the stomach. The GPR38 mRNA expression was also higher in the proximal corpus than in the other sections, and the lowest expression was observed in the antrum. GPR38 mRNA expression varied with low expression in the mucosal layer and high expression in the muscle layer. Additionally, motilin-induced contractions in each dissected part of the stomach were inhibited by tetrodotoxin and atropine pretreatment. These results suggest that motilin reactivity is not consistent throughout the stomach, and an area of the proximal corpus including the cardia is the most sensitive to motilin.

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Section: Introductionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 55%

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

et al. 2016

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“…5). It is noteworthy that motilin began to evoke gastric contraction of S. murinus at 1 nM but was unable to do so at 100 pM in vitro (54). Stomach contractions occurred in response to 100 pM ghrelin after pretreatment with motilin alone, but only small contractions occurred when stomachs were pretreated with [D-Lys-3]-GHRP-6 or G5-1 in conjunction with motilin, even at high doses of ghrelin.…”

Section: Resultsmentioning

confidence: 94%

In vitro selection of a peptide antagonist of growth hormone secretagogue receptor using cDNA display

Ueno

Yoshida

Mondal

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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G protein-coupled receptors (GPCRs) are major drug targets, and their ligands are currently being explored and developed by many pharmaceutical companies and independent researchers. Class A (rhodopsin-like) GPCRs compose a predominant GPCR family; therefore, class A GPCR ligands are in demand. Growth hormone secretagogue receptor (GHS-R) is a class A GPCR that stimulates food intake by binding to its peptide ligand, ghrelin. Therefore, antagonists of GHS-R are expected to exert antiobesity function. In this article, we describe the use of cDNA display to screen for successfully and identify an antagonistic peptide of GHS-R. The antagonistic peptide inhibited the ghrelin-induced increase in intracellular Ca 2þ in vitro (IC 50 ¼ approximately 10 μM) and repressed the contraction of isolated animal stomach in response to ghrelin. Furthermore, peripheral administration of the peptide inhibited the food intake of mice. This work provides new insight into the development of antiobesity drugs and describes a method for the discovery of unique peptide ligands for class A GPCRs.aptamer | in vitro display | peptide drug | ligand screening | cell-based selection

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“…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.…”

Section: Figurementioning

confidence: 99%

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

Deloose¹,

Vos²,

Janssen³

et al. 2016

The American Journal of Clinical Nutrition

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Background: Motilin-induced phase III contractions have been identified as a hunger signal. These phase III contractions occur as part of the migrating motor complex (MMC), a contractility pattern of the gastrointestinal tract during fasting. The mechanism involved in this association between subjective hunger feelings and gastrointestinal motility during the MMC is largely unknown, however, as is its ability to stimulate food intake. Objectives: We sought to 1) investigate the occurrence of hunger peaks and their relation to phase III contractions, 2) evaluate whether this relation was cholinergically driven, and 3) assess the ability of the motilin receptor agonist erythromycin to induce food intake. Design: An algorithm was developed to detect hunger peaks. The association with phase III contractions was studied in 14 healthy volunteers [50% men; mean 6 SEM age: 25 6 2 y; mean 6 SEM body mass index (BMI; in kg/m 2 ): 23 6 1]. The impact of pharmacologically induced phase III contractions on the occurrence of hunger peaks and the involvement of a cholinergic pathway were assessed in 14 healthy volunteers (43% men; age: 29 6 3 y; BMI: 23 6 1). Last, the effect of erythromycin administration on food intake was examined in 15 healthy volunteers (40% men; age: 28 6 3 y; BMI: 22 6 1). Results: The occurrence of hunger peaks and their significant association with phase III contractions was confirmed (P , 0.0001). Pharmacologically induced phase III contractions were also significantly associated with hunger peaks (P , 0.05), and this association involved a cholinergic pathway. Administering erythromycin significantly stimulated food intake compared with placebo (53% 6 13% compared with 10% 6 5%; P , 0.05). Conclusions: Motilin-induced phase III contractions induced hunger feelings through a cholinergic pathway. Moreover, erythromycin stimulated food intake, suggesting a physiologic role of motilin as an orexigenic signal from the gastrointestinal tract. This trial was registered at www.clinicaltrials.gov as NCT02633579.Am J Clin Nutr 2016;103:730-7.

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Myenteric neural network activated by motilin in the stomach of Suncus murinus (house musk shrew)

Abstract: The results indicate that motilin directly stimulates and modulates suncus gastric contraction through cholinergic, adrenergic, serotonergic, opioidergic, and NO neurons in the myenteric plexus.

Cited by 27 publications

References 51 publications

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

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

In vitro selection of a peptide antagonist of growth hormone secretagogue receptor using cDNA display

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

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