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

Dudani, Amrita; Aizawa, Sayaka; Zhi, Guang; Tanaka, Toru; Jogahara, Takamichi; Sakata, Ichiro; Sakai, Takafumi

doi:10.1007/s00360-016-0985-1

Cited by 4 publications

(5 citation statements)

References 47 publications

(60 reference statements)

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“…Similar results have been reported in shrew and human stomachs [29,30], suggesting that the motilin-induced contractile response is anatomically region-specific.…”

Section: Discussionsupporting

confidence: 87%

Characterization of the gastric motility response to human motilin and erythromycin in human motilin receptor-expressing transgenic mice

Kato

Takahashi

Shindo

et al. 2018

Preprint

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Motilin is a gastrointestinal peptide hormone that stimulates gastrointestinal motility. Motilin is produced primarily in the duodenum and jejunum. Motilin receptors (MTLRs) are G proteincoupled receptors that may represent a clinically useful pharmacological target as they can be activated by erythromycin. The functions of motilin are highly species-dependent and remain poorly understood. As a functional motilin system is absent in rodents such as rats and mice, these species are not commonly used for basic studies. In this study, we examine the usefulness of human MTLR-overexpressing transgenic (hMTLR-Tg) mice by identifying the mechanisms of the gastric motor response to human motilin and erythromycin.The distribution of hMTLR was examined immunohistochemically in male wild-type (WT) and hMTLR-Tg mice. The contractile response of gastric strips was measured isometrically in an organ bath, while gastric emptying was determined using phenol red.hMTLR expression was abundant in the gastric smooth muscle layer but more potently expressed in the myenteric plexus of hMTLR-Tg mice but not WT mice. hMTLR was not colocalized with vesicular acetylcholine transporter, a marker of cholinergic neurons in the myenteric plexus. Treatment with human motilin and erythromycin caused concentrationdependent contraction of gastric strips obtained from hMTLR-Tg mice but not from WT mice. 2The contractile response to human motilin and erythromycin in hMTLR-Tg mice was affected by neither atropine nor tetrodotoxin and was totally absent in Ca 2+ -free conditions. Furthermore, intraperitoneal injection of erythromycin significantly promoted gastric emptying in hMTLR-Tg mice but not in WT mice.Human motilin and erythromycin stimulate the gastric motor response in hMTLR-Tg mice. This action is mediated by direct contraction of smooth muscle via the influx of extracellular Ca 2+ . Thus, hMTLR-Tg mice may be useful for the evaluation of MTLR agonists as gastric prokinetic agents.

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“…Similar results have been reported in shrew and human stomachs [29,30], suggesting that the motilin-induced contractile response is anatomically region-specific.…”

Section: Discussionsupporting

confidence: 87%

Characterization of the gastric motility response to human motilin and erythromycin in human motilin receptor-expressing transgenic mice

Kato

Takahashi

Shindo

et al. 2018

Preprint

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“…In contrast, Dudani et al . [30] reported that the contractile response to motilin in house shrew was more prominent in the gastric fundus than in the antrum. In general, the contractile response in mice to various stimulation such as acetylcholine, serotonin, and electrical field stimulation was more prominent in the gastric fundus than in the antrum [31].…”

Section: Discussionmentioning

confidence: 99%

Characterization of the gastric motility response to human motilin and erythromycin in human motilin receptor-expressing transgenic mice

et al. 2019

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Motilin is a gastrointestinal peptide hormone that stimulates gastrointestinal motility. Motilin is produced primarily in the duodenum and jejunum. Motilin receptors (MTLRs) are G protein-coupled receptors that may represent a clinically useful pharmacological target as they can be activated by erythromycin. The functions of motilin are highly species-dependent and remain poorly understood. As a functional motilin system is absent in rodents such as rats and mice, these species are not commonly used for basic studies. In this study, we examine the usefulness of human MTLR-overexpressing transgenic (hMTLR-Tg) mice by identifying the mechanisms of the gastric motor response to human motilin and erythromycin. The distribution of hMTLR was examined immunohistochemically in male wild-type (WT) and hMTLR-Tg mice. The contractile response of gastric strips was measured isometrically in an organ bath, while gastric emptying was determined using phenol red. hMTLR expression was abundant in the gastric smooth muscle layer. Interestingly, higher levels of hMTLR expression were observed in the myenteric plexus of hMTLR-Tg mice but not WT mice. hMTLR was not co-localized with vesicular acetylcholine transporter, a marker of cholinergic neurons in the myenteric plexus. Treatment with human motilin and erythromycin caused concentration-dependent contraction of gastric strips obtained from hMTLR-Tg mice but not from WT mice. The contractile response to human motilin and erythromycin in hMTLR-Tg mice was affected by neither atropine nor tetrodotoxin and was totally absent in Ca 2+ -free conditions. Furthermore, intraperitoneal injection of erythromycin significantly promoted gastric emptying in hMTLR-Tg mice but not in WT mice. Human motilin and erythromycin stimulate gastric smooth muscle contraction in hMTLR-Tg mice. This action is mediated by direct contraction of smooth muscle via the influx of extracellular Ca 2+ . Thus, hMTLR-Tg mice may be useful for the evaluation of MTLR agonists as gastric prokinetic agents.

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“…Motilin, SP, SS, and VIP are closely associated with gastric functions. MOT and SP will be increased in GU development ( Dudani et al, 2016 ). In conversely, SS ( Coskun et al, 2013 ) and VIP ( Kasacka et al, 2015 ) have protective functions for stomach.…”

Section: Discussionmentioning

confidence: 99%

“…Motilin (MOT) modulates gastric contraction via cholinergic, adrenergic, serotonergic, and NO neurons ( Mondal et al, 2011 ), and is associated with emptying the stomach during the interdigestive period ( Dudani et al, 2016 ). Substance P (SP) belongs to an undecapeptide member of the tachykinin neuropeptide family.…”

Section: Methodsmentioning

confidence: 99%

1-Deoxynojirimycin (DNJ) Ameliorates Indomethacin-Induced Gastric Ulcer in Mice by Affecting NF-kappaB Signaling Pathway

Piao¹,

Sui

et al. 2018

Front. Pharmacol.

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Gastric ulcer (GU) is a main threat to public health. 1-Deoxynojirimycin (DNJ) has antioxidant and anti-inflammatory properties and may prevent GU but related mechanism remains unclear. DNJ was extracted from the supernatants of Bacillus subtilis by using ethanol and purified by using CM-Sepharose chromatography. A GU mouse model was induced by indomethacin. The functional role of DNJ in GU mice was explored by measuring the main molecules in the NF-KappaB pathway. After the model establishment, 40 GU mice were evenly assigned into five categories: IG (received vehicle control), LG (10 μg DNJ daily), MG (20 μg DNJ daily), HG (40 μg DNJ daily), and RG (0.5 mg ranitidine daily). Meanwhile, eight healthy mice were assigned as a control group (CG). After 1-month therapy, weight and gastric volume were investigated. The levels of serum inflammatory cytokines (IL-6 and TNF-α), antioxidant indices [superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)], and oxidant biomarker malondialdehyde (MDA) were examined via ELISA. Meanwhile, inflammatory cytokine (IL-6 and TNF-α) levels, and key molecules (NF-κB p65), cyclooxygenase 1 (COX-1 and COX2) involved in NF-κB pathway, were analyzed by using Western Blot. COX-1 and COX-2 levels were further measured by immunohistochemistry. The effects of DNJ on gastric functions were explored by measuring the changes of Motilin (MOT), Substance P (SP), Somatostatin (SS), and Vasoactive intestinal peptide (VIP) in GU mouse models with ELISA Kits. The results indicated that DNJ prevented indomethacin-caused increase of gastric volume. DNJ improved histopathology of GU mice when compared with the mice from IG group (P < 0.05). DNJ consumption decreased the levels of IL-6 and TNF-α (P < 0.05). DNJ increased antioxidant indices of GU mice by improving the activities of SOD, CAT and reduced GSH, and reduced MDA levels (P < 0.05). DNJ increased the levels of prostaglandin E2, COX-1, COX2, and reduced the levels of and NF-κB p65 (P < 0.05). DNJ showed protection for gastric functions of GU mice by reducing the levels of MOT and SP, and increasing the levels of SS and VIP. DNJ treatment inactivates NF-κB signaling pathway, and increases anti-ulceration ability of the models.

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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

Cited by 4 publications

References 47 publications

Characterization of the gastric motility response to human motilin and erythromycin in human motilin receptor-expressing transgenic mice

Characterization of the gastric motility response to human motilin and erythromycin in human motilin receptor-expressing transgenic mice

Characterization of the gastric motility response to human motilin and erythromycin in human motilin receptor-expressing transgenic mice

1-Deoxynojirimycin (DNJ) Ameliorates Indomethacin-Induced Gastric Ulcer in Mice by Affecting NF-kappaB Signaling Pathway

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