House musk shrew (Suncus murinus, order: Insectivora) as a new model animal for motilin study

Tsutsui, Chihiro; Kajihara, Kie; Yanaka, Takatsugu; Sakata, Ichiro; Itoh, Zen; Oda, Sen-ichi; Sakai, Takafumi

doi:10.1016/j.peptides.2008.10.006

Cited by 59 publications

(45 citation statements)

References 40 publications

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“…These results strongly suggest that rats and mice do not produce motilin and that rodents are therefore not suitable animals for motilin study. On the other hand, we previously confirmed the production of physiological active motilin in the suncus by using molecular cloning and an in vitro organ bath experiment, and we also demonstrated that suncus motilin is expressed in the upper small intestine (43). In the present study, we found that the stomach and small intestine of the conscious suncus showed spontaneous gastric phase III contractions every 80 -150 min, almost the same intervals as those found in humans and dogs.…”

Section: Discussionsupporting

confidence: 84%

“…Because there is no cecum in the suncus, it is difficult to distinguish the small intestine and colon. Therefore, in this study, we divided the intestine into six equal segments (intestines 1-6) as previously reported (15,43). All procedures were approved and performed in accordance with the Saitama University Committee on Animal Research.…”

Section: Methodsmentioning

confidence: 99%

“…The suncus is a small mammal that belongs to the order Insectivora, family Soricidae, genus Suncus (3). We previously reported the complete cDNA sequences and tissue distribution of motilin and ghrelin in the suncus (15,43), and reproducible contractile responses of the suncus stomach to suncus or human motilin were found in an in vitro organ bath experiment (43). …”

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confidence: 96%

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Physiological characteristics of gastric contractions and circadian gastric motility in the free-moving conscious house musk shrew (Suncus murinus)

Sakahara

Xie

Koike

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Physiological characteristics of gastric contractions and circadian gastric motility in the free-moving conscious house musk shrew (Suncus murinus). Am J Physiol Regul Integr Comp Physiol 299: R1106 -R1113, 2010. First published August 4, 2010 doi:10.1152/ajpregu.00278.2010.-Although many studies have demonstrated the physiological action of motilin on the migrating motor complex, the precise mechanisms remain obscure. To obtain new insights into the mechanisms, we focused on the house musk shrew (Suncus murinus, suncus used as a laboratory name) as a small model animal for in vivo motilin study, and we studied the physiological characteristics of suncus gastrointestinal motility. Strain gauge transducers were implanted on the serosa of the gastric body and duodenum, and we recorded gastrointestinal contractions in the free-moving conscious suncus and also examined the effects of intravenous infusion of various agents on gastrointestinal motility. During the fasted state, the suncus stomach and duodenum showed clear migrating phase III contractions (intervals of 80 -150 min) as found in humans and dogs. Motilin (bolus injection, 100-300 ng/kg; continuous infusion, 10-100 ng · kg Ϫ1 · min Ϫ1 ) and erythromycin (80 g·kg Ϫ1 · min Ϫ1 ) induced gastric phase III contractions, and motilin injection also increased the gastric motility index in a dose-dependent manner (P Ͻ 0.05, vs. saline). Pretreatment with atropine completely abolished the motilin-induced gastric phase III contractions. On the other hand, in the free-feeding condition, the suncus showed a relatively long fasting period in the light phase followed by spontaneous gastric phase III contractions. The results suggest that the suncus has almost the same gastrointestinal motility and motilin response as those found in humans and dogs, and we propose the suncus as a new small model animal for studying gastrointestinal motility and motilin in vivo.suncus; migrating motor complex; motilin; ghrelin; gastric motility DURING A FASTED STATE, THE stomach and small intestine undergo a temporally coordinated cyclic motor pattern known as migrating motor complex (MMC) in dogs (38) and humans (44). It has been established that these coordinated contractions consist of three phases, phase I (period of motor quiescence), phase II (period of preceding irregular contractions), and phase III (period of clustered potent contractions), and the MMC is stimulated by endogenous motilin that is released in the fasted state.Motilin was originally purified from porcine intestinal mucosa in the 1970s, and its molecular structure was determined to be a 22-amino-acid polypeptide. It has been demonstrated that plasma motilin is released at ϳ100-min intervals at the interdigestive state (20,21). Physiological study of motilin in vivo has been mainly performed by using dogs and humans, and endogenous motilin and exogenous motilin have been shown to induce phase III contractions through the cholinergic pathway because atropine pretreatment completely abolished the motilin-induced contra...

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Section: Discussionsupporting

confidence: 84%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 96%

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Physiological characteristics of gastric contractions and circadian gastric motility in the free-moving conscious house musk shrew (Suncus murinus)

Sakahara

Xie

Koike

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Motilin is a peptide hormone that stimulates gastric contraction similarly to ghrelin, and it is not expressed in rodents such as mice and rats (52). Suncus murinus is a small mammal that expresses both motilin and ghrelin; thus, it can be used to study motilin-ghrelin family peptides (53). Suncus stomachs pretreated with low concentrations of motilin (100 pM) underwent contraction in response to ghrelin in a dose-dependent manner (Fig.…”

Section: Resultsmentioning

confidence: 99%

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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“…S. murinus is a small animal model of interest for gastrointestinal research because it has an emetic reflex that is lacking in rodents. 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).…”

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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House musk shrew (Suncus murinus, order: Insectivora) as a new model animal for motilin study

Cited by 59 publications

References 40 publications

Physiological characteristics of gastric contractions and circadian gastric motility in the free-moving conscious house musk shrew (Suncus murinus)

Physiological characteristics of gastric contractions and circadian gastric motility in the free-moving conscious house musk shrew (Suncus murinus)

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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