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The effects of motilin and receptor antagonists on the latter half of PPC in the suncus. A continuous infusion of vehicle or MA-2029 (1 mg kg À1 h À1 ) starting at 120 min after feeding did not change gastric contractions or motility index (a, b, e). On the other hand, a continuous infusion of D-Lys 3-GHRP6 immediately inhibited gastric contractions in the latter half of the PPC period (c), and the motility index during infusion was significantly decreased (g). Administration of each receptor antagonist in the latter half of the PPCs prolonged the duration from feeding to PPGC (b, c, f, h). Administration of motilin (300 ng kg À1 IV) in the latter half of the PPCs, at 120 min after feeding, induced strong phase III-like contractions, and the PPCs rapidly changed to phase I contractions (d). Each histogram represents the mean AE SEM (n = 3). Statistical analysis was performed using a paired t-test. **P < 0.01, *P < 0.05 vs. vehicle; *: phase III contractions. #: PPGC.
Source publication
Aim:
Stomach contractions show two types of specific patterns in many species, i.e., migrating motor contraction (MMC) and postprandial contractions (PPCs), in the fasting and fed state, respectively. We found gastric PPCs terminated with migrating strong contractions in humans, dogs, and suncus. In this study, we reveal the detailed characteristi...
Contexts in source publication
Context 1
... MA-2029 did not change gastric motility (Fig. 5b, e), D-Lys 3 -GHRP6 infusion significantly attenuated gastric contraction in the latter half of the PPCs (Fig. 5c, g). During continuous infusion of MA- 2029 or D-Lys 3 -GHRP6, the PPGC did not occur and duration from onset of postprandial motility/feeding to the end of PPGC was significantly prolonged (Fig. 5b, c, f, h). Administration ...
Context 2
... MA-2029 did not change gastric motility (Fig. 5b, e), D-Lys 3 -GHRP6 infusion significantly attenuated gastric contraction in the latter half of the PPCs (Fig. 5c, g). During continuous infusion of MA- 2029 or D-Lys 3 -GHRP6, the PPGC did not occur and duration from onset of postprandial motility/feeding to the end of PPGC was significantly prolonged (Fig. 5b, c, f, h). Administration of motilin in the lat- ter half of PPC (120 min after feeding) evoked phase III-like contractions (Fig. 5d). The MI ...
Context 3
... did not change gastric motility (Fig. 5b, e), D-Lys 3 -GHRP6 infusion significantly attenuated gastric contraction in the latter half of the PPCs (Fig. 5c, g). During continuous infusion of MA- 2029 or D-Lys 3 -GHRP6, the PPGC did not occur and duration from onset of postprandial motility/feeding to the end of PPGC was significantly prolonged (Fig. 5b, c, f, h). Administration of motilin in the lat- ter half of PPC (120 min after feeding) evoked phase III-like contractions (Fig. 5d). The MI during 5 min after administration in the latter half of the PPC per- iod was significantly increased as compared with the (1 mg kg À1 h À1 ) or D-Lys 3 -GHRP6 (6 mg kg À1 h À1 ) started at 10 min after ...
Context 4
... half of the PPCs (Fig. 5c, g). During continuous infusion of MA- 2029 or D-Lys 3 -GHRP6, the PPGC did not occur and duration from onset of postprandial motility/feeding to the end of PPGC was significantly prolonged (Fig. 5b, c, f, h). Administration of motilin in the lat- ter half of PPC (120 min after feeding) evoked phase III-like contractions (Fig. 5d). The MI during 5 min after administration in the latter half of the PPC per- iod was significantly increased as compared with the (1 mg kg À1 h À1 ) or D-Lys 3 -GHRP6 (6 mg kg À1 h À1 ) started at 10 min after feeding, showed no effect on sponta- neous gastric contractions (a, b, c). No significant differences were found in motility ...
Citations
... On the other hand, postprandial contractions (PPCs) that are initiated immediately after eating are composed of a rhythmic contraction and a subsequent postprandial giant contraction (PPGC). In the stomach, it has been demonstrated that the latter half of the PPCs and the PPGC had the same properties as those of phase II and phase III contractions of MMC, respectively (3). Due to the lack of a suitable animal model to mimic human responses, the detailed mechanisms of gastric motility, especially inhibitory mechanisms, remain to be elucidated. ...
... The definition of each contraction type and the statistical analyses performed followed those used in a previous study (3). PPCs were defined as the continuous irregular and low-amplitude contractions that began after feeding and lasted to the initiation of phase I of MMC, and PPGCs were defined as the strong contractions that occurred at the end of the PPCs, prior to phase I of MMC. ...
Gastric contractions show two specific patterns in many species, migrating motor contractions (MMC) and postprandial contractions (PPCs), that occur in the fasted and fed states, respectively. In this study, we examined the role of somatostatin (SST) in gastric motility both in vivo and in vitro using the Asian house shrew (Suncus murinus). We performed in vivo recordings of gastric motility and in vitro organ bath experiments using S. murinus, which was recently established as a small laboratory animal for use in tests of gastrointestinal motility. SST (1.65 µg kg⁻¹ min⁻¹) was intravenously administered during phase II of MMC and PPCs. Next, the effect of SST on motilin-induced gastric contractions at phase I of MMC was measured. Cyclosomatostatin (CSST), an SST receptor antagonist, was administered at the peak of phase III of MMC. In addition, the effect of SST (10⁻¹¹–10⁻⁹ M) on motilin-induced gastric contractions was evaluated using an organ bath experiment in vitro. In conscious, free-moving S. murinus, the administration of SST decreased the occurrence of the spontaneous phase II of MMC and PPCs. Pretreatment with SST and octreotide suppressed the induction of motilin-induced gastric contractions both in vivo and in vitro. Administration of CSST before the peak of spontaneous phase III contractions had no effect on gastric contractions. Endogenous SST is not involved in the regulation of gastric MMC and PPCs, but exogenous SST suppresses spontaneous gastric contractions. Thus, SST would be good for treating abnormal gastrointestinal motility disorders.
Diabetic gastroparesis (DGP) is a common complication of diabetes mellitus, marked by gastrointestinal motility disorder, a delayed gastric emptying present in the absence of mechanical obstruction. Clinical manifestations include postprandial fullness and epigastric discomfort, bloating, nausea, and vomiting. DGP may significantly affect the quality of life and productivity of patients. Research on the relationship between gastrointestinal dynamics and DGP has received much attention because of the increasing prevalence of DGP. Gastrointestinal motility disorders are closely related to a variety of factors including the absence and destruction of interstitial cells of Cajal, abnormalities in the neuro-endocrine system and hormone levels. Therefore, this study will review recent literature on the mechanisms of DGP and gastrointestinal motility disorders as well as the development of prokinetic treatment of gastrointestinal motility disorders in order to give future research directions and identify treatment strategies for DGP.
Motilin is an important hormonal regulator in the migrating motor complex (MMC). Free fatty acid receptor-1 (FFAR1, also known as GPR40) has been reported to stimulate motilin release in human duodenal organoids. However, how FFAR1 regulates gastric motility in vivo is unclear. This study investigated the role of FFAR1 in the regulation of gastric contractions and its possible mechanism of action using Suncus murinus. Firstly, intragastric administration of oleic acid (C18:1, OA), a natural ligand for FFAR1, stimulated phase II-like contractions, followed by phase III-like contractions in the fasted state, and the gastric emptying rate was accelerated. The administration of GW1100, an FFAR1 antagonist, inhibited the effects of OA-induced gastric contractions. Intravenous infusion of a ghrelin receptor antagonist (DLS) or serotonin 4 (5-HT4) receptor antagonist (GR125487) inhibited phase II-like contractions and prolonged the onset of phase III-like contractions induced by OA. MA-2029, a motilin receptor antagonist, delayed the occurrence of phase III-like contractions. In vagotomized suncus, OA did not induce phase II-like contractions. In addition, OA promoted gastric emptying through a vagal pathway during the postprandial period. However, OA did not directly act on the gastric body to induce contractions in vitro. In summary, this study indicates that ghrelin, motilin, 5-HT, and the vagus nerve are involved in the role of FFAR1 regulating MMC. Our findings provide novel evidence for the involvement of nutritional factors in the regulation of gastric motility.
In a fasting gastrointestinal tract, a characteristic cyclical rhythmic migrating motor complex (MMC) occur that comprises of three phases: I, II, and III. Among these, phase III contractions propagate from the stomach to the lower intestine in mammals, including humans, dogs, and Suncus murinus (suncus). Apart from the phase III of MMC propagating from the stomach, during the gastric phase II, small intestine-originated strong contractions propagate to the lower small intestine; however, the mechanism of contractions originating in the small intestine has not been clarified. In this study, we aimed to elucidate the role of cholecystokinin (CCK) in small intestinal motility. Administration of sulfated CCK-8 in phase I induced phase II-like contractions in the small intestine, which lasted for approximately 10-20 min and then returned to the baseline, while no change was observed in the stomach. Contractions of small intestine induced by CCK-8 were abolished by lorglumide, a CCK1 receptor antagonist. Gastrin, a ligand for the CCK2 receptor, evoked strong contractions in the stomach, but did not induce contractions in the small intestine. To examine the effect of endogenous CCK on contractions of small intestinal origin, lorglumide was administered during phase II. However, there was no change in the duodenal motility pattern, and strong contractions of small intestinal origin were not abolished by treatment with lorglumide. These results suggest that exogenous CCK stimulates contractions of small intestine via CCK1 receptors, whereas endogenous CCK is not involved in the strong contractions of small intestinal origin.
Background
The aim of this study was to investigate the fundamental mechanisms of colonic motility in the house musk suncus (Suncus murinus) as an established animal model of gut motility.
Methods
To measure gut motility in free‐moving conscious suncus, strain gauge force transducers were implanted on the serosa of the colon and gastric body.
Key Results
We recorded diurnal changes in colonic motility and observed the relationship between feeding and colonic motility. Giant migrating contractions (GMCs) of the colon were invariably detected during defecation and tended to increase during the dark period, thereby indicating that colonic motility has a circadian rhythm. Given that GMCs in the suncus were observed immediately after feeding during the dark period, we assume the occurrence of a gastrocolic reflex in suncus, similar to that observed in humans and dogs. We also examined the factors that regulate suncus GMCs. Intravenous administration of 5‐HT (100 µg/kg), substance P (10 and 100 µg/kg), calcitonin gene‐related peptide (10 µg/kg), and α2 adrenergic receptor antagonist yohimbine (0.5, 1, and 3 mg/kg) induced GMC‐like contractions, as did intragastric and intracolonic administration of the transient receptor potential vanilloid 1 agonist, capsaicin (1 mg/kg).
Conclusions & Inferences
These results indicate that the fundamental mechanisms of colonic motility in suncus are similar to those in humans and dogs, and we thus propose that suncus could serve as a novel small animal model for studying colonic motility.
Motilin, produced in endocrine cells in the mucosa of the upper intestine, is an important regulator of gastrointestinal (GI) motility and mediates the phase III of interdigestive migrating motor complex (MMC) in the stomach of humans, dogs and house musk shrews through the specific motilin receptor (MLN-R). Motilin-induced MMC contributes to the maintenance of normal GI functions and transmits a hunger signal from the stomach to the brain. Motilin has been identified in various mammals, but the physiological roles of motilin in regulating GI motility in these mammals are well not understood due to inconsistencies between studies conducted on different species using a range of experimental conditions. Motilin orthologs have been identified in non-mammalian vertebrates, and the sequence of avian motilin is relatively close to that of mammals, but reptile, amphibian and fish motilins show distinctive different sequences. The MLN-R has also been identified in mammals and non-mammalian vertebrates, and can be divided into two main groups: mammal/bird/reptile/amphibian clade and fish clade. Almost 50 years have passed since discovery of motilin, here we reviewed the structure, distribution, receptor and the GI motility regulatory function of motilin in vertebrates from fish to mammals.
ABSTRACT
Alteration in the gastrointestinal (GI) motility and transit comprises an important component of the functional gastrointestinal disorders (FGID). Available animal GI motility and transit models are to study symptoms (delayed gastric emptying, constipation, diarrhea) rather than biological markers to develop an effective treatment that targets the underlying
mechanism of altered GI motility in patients. Animal data generated from commonly used methods in human-like scintigraphy, breath test and wireless motility capsule may directly translate to clinic. However, species differences in the control mechanism or pharmacological responses of GI motility may compromise the predictive and
translational value of the preclinical data to human. In this review we aim to provide a summary on animal models used to mimic GI motility alteration in FGID, and the impact of the species differences in the physiological and pharmacological responses on the translation of animal GI motility and transit data to human.
Keywords: gastrointestinal motility, functional gastrointestinal disorders, animal model.
