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Takafumi Sakai - One of the best experts on this subject based on the ideXlab platform.
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identification and characterization of an antimicrobial peptide lysozyme from Suncus murinus
Cell and Tissue Research, 2019Co-Authors: Shota Takemi, Takafumi Sakai, Toru Tanaka, Shiomi Ojima, Ichiro SakataAbstract:Lysozyme is one of the most prominent antimicrobial peptides and has been identified from many mammalian species. However, this enzyme has not been studied in the order Insectivora, which includes the most primitive placental mammals. Here, we done the lysozyme cDNA from Suncus murinus (referred to as Suncus, its laboratory name) and compare the predicted amino acid sequence to those from other mammalian species. Quantitative PCR analysis revealed a relatively higher expression of this gene in the spleen and gastrointestinal tract of Suncus. The lysozyme-immunopositive (ip) cells were found mainly in the red pulp of the spleen and in the mucosa of the whole small intestine, including the follicle-associated epithelium and subepithelial dome of Peyer’s patches. The lysozyme-ip cells in the small intestine were mostly distributed in the intestinal crypt, although lysozyme-expressing cells were found not only in the crypt but also in the villi. On the other hand, only a few lysozyme-ip cells were found in the villi and some granules showing intense fluorescence were located toward the lumen. As reported for other mammals, Ki67-ip cells were localized in the crypt and did not co-localize with the lysozyme-ip cells. Moreover, fasting induced a decrease in the mRNA levels of lysozyme in the intestine of Suncus. In conclusion, we firstly identified the lysozyme mRNA sequence, clarified expression profile of lysozyme transcripts in Suncus and found a unique distribution of lysozyme-producing cells in the Suncus intestine.
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study of termination of postprandial gastric contractions in humans dogs and Suncus murinus role of motilin and ghrelin induced strong contraction
Acta Physiologica, 2018Co-Authors: Takashi Mikami, Takamichi Jogahara, Ichiro Sakata, Toru Tanaka, Shota Takemi, H O Diaztartera, Per M Hellstrom, E Mochiki, Sachiko Tsuda, Takafumi SakaiAbstract:Aim Stomach contractions show two types of specific patterns in many species, that is migrating motor contraction (MMC) and postprandial contractions (PPCs), in the fasting and fed states respectively. We found gastric PPCs terminated with migrating strong contractions in humans, dogs and Suncus. In this study, we reveal the detailed characteristics and physiological implications of these strong contractions of PPC. Methods Human, Suncus and canine gastric contractions were recorded with a motility-monitoring ingestible capsule and a strain-gauge force transducer. The response of motilin and ghrelin and its receptor antagonist on the contractions were studied by using free-moving Suncus. Results Strong gastric contractions were observed at the end of a PPC in human, dog and Suncus models, and we tentatively designated this contraction to be a postprandial giant contraction (PPGC). In the Suncus, the PPGC showed the same property as those of a phase III contraction of MMC (PIII-MMC) in the duration, motility index and response to motilin or ghrelin antagonist administration. Ghrelin antagonist administration in the latter half of the PPC (LH-PPC) attenuated gastric contraction prolonged the duration of occurrence of PPGC, as found in PII-MMC. Conclusion It is thought that the first half of the PPC changed to PII-MMC and then terminated with PIII-MMC, suggesting that PPC consists of a digestive phase (the first half of the PPC) and a discharge phase (LH-PPC) and that LH-PPC is coincident with MMC. In this study, we propose a new approach for the understanding of postprandial contractions.
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RESEARCH ARTICLE Motilin Stimulates Gastric Acid Secretion in Coordination with Ghrelin in Suncus murinus
2016Co-Authors: Chayon Goswami, Takafumi Sakai, Toru Tanaka, Yoshiaki Shimada, Makoto Yoshimura, Ichi Oda, Ichiro SakataAbstract:Motilin and ghrelin constitute a peptide family, and these hormones are important for the regulation of gastrointestinal motility. In this study, we examined the effect of motilin and ghrelin on gastric acid secretion in anesthetized Suncus (house musk shrew, Suncus muri-nus), a ghrelin- and motilin-producing mammal. We first established a gastric lumen-perfu-sion system in the Suncus and confirmed that intravenous (i.v.) administration of histamine (1 mg/kg body weight) stimulated acid secretion. Motilin (0.1, 1.0, and 10 μg/kg BW) stimu-lated the acid output in a dose-dependent manner in Suncus, whereas ghrelin (0.1, 1.0, and 10 μg/kg BW) alone did not induce acid output. Furthermore, in comparison with the vehicle administration, the co-administration of low-dose (1 μg/kg BW) motilin and ghrelin signifi-cantly stimulated gastric acid secretion, whereas either motilin (1 μg/kg BW) or ghrelin (1 μg/kg BW) alone did not significantly induce gastric acid secretion. This indicates an addi-tive role of ghrelin in motilin-induced gastric acid secretion. We then investigated the path-ways of motilin/motilin and ghrelin-stimulated acid secretion using receptor antagonists. Treatment with YM 022 (a CCK-B receptor antagonist) and atropine (a muscarinic acetyl-choline receptor antagonist) had no effect on motilin or motilin-ghrelin co-administration-induced acid output. In contrast, famotidine (a histamine H2 receptor antagonist) completely inhibited motilin-stimulated acid secretion and co-administration of motilin and ghrelin induced gastric acid output. This is the first report demonstrating that motilin stimulates gas-tric secretion in mammals. Our results also suggest that motilin and co-administration of motilin and ghrelin stimulate gastric acid secretion via the histamine-mediated pathway in Suncus
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The Role of the Vagus Nerve in the Migrating Motor Complex and Ghrelin- and Motilin-Induced Gastric Contraction in Suncus
2016Co-Authors: Yuki Miyano, Takamichi Jogahara, Sayaka Aizawa, Ichiro Sakata, Toru Tanaka, Kayuri Kuroda, Reiko Kurotani, Takafumi SakaiAbstract:The upper gastrointestinal (GI) tract undergoes a temporally coordinated cyclic motor pattern known as the migrating motor complex (MMC) in both dogs and humans during the fasted state. Feeding results in replacement of the MMC by a pattern of noncyclic, intermittent contractile activity termed as postprandial contractions. Although the MMC is known to be stimulated by motilin, recent studies have shown that ghrelin, which is from the same peptide family as motilin, is also involved in the regulation of the MMC. In the present study, we investigated the role of the vagus nerve on gastric motility using conscious Suncus—a motilin- and ghrelin-producing small animal. During the fasted state, cyclic MMC comprising phases I, II, and III was observed in both sham-operated and vagotomized Suncus; however, the duration and motility index (MI) of phase II was significantly decreased in vagotomized animals. Motilin infusion (50 ng?kg21?min21 for 10 min) during phase I had induced phase III–like contractions in both sham-operated and vagotomized animals. Ghrelin infusion (0.1, 0.3, 1, 3, or 10 mg?kg21?min21 for 10 min) enhanced the amplitude of phase II MMC in sham-operated animals, but not in vagotomized animals. After feeding, phase I was replaced by postprandial contractions, and motilin infusion (50 ng?kg21?min21 for 10 min) did not induce phase III–like contractions in sham-operated Suncus. However, in vagotomized Suncus, feeding did not evoke postprandial contractions, but exogenous motilin injection strongly induced phase III–like contractions, as noted during the phase I period. Thus, the results indicate that ghrelin stimulates phase II o
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motilin stimulates pepsinogen secretion in Suncus murinus
Biochemical and Biophysical Research Communications, 2015Co-Authors: Chayon Goswami, Takamichi Jogahara, Takafumi Sakai, Toru Tanaka, Ichiro SakataAbstract:Abstract Motilin and ghrelin are gastrointestinal hormones that stimulate the migrating motor complex (MMC) of gastrointestinal motility during the fasting state. In this study, we examined the effect of motilin and ghrelin on pepsinogen secretion in anesthetized Suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin-producing mammal. By using a gastric lumen-perfusion system, we found that the intravenous administration of carbachol and motilin stimulated pepsinogen secretion, the latter in a dose-dependent manner, whereas ghrelin had no effect. We then investigated the pathways of motilin-induced pepsinogen secretion using acetylcholine receptor antagonists. Treatment with atropine, a muscarinic acetylcholine receptor antagonist, completely inhibited both carbachol and motilin-induced pepsinogen secretion. Motilin-induced pepsinogen secretion was observed in the vagotomized Suncus. This is the first report demonstrating that motilin stimulates pepsinogen secretion, and suggest that this effect occurs through a cholinergic pathway in Suncus.
Ichiro Sakata - One of the best experts on this subject based on the ideXlab platform.
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identification and characterization of an antimicrobial peptide lysozyme from Suncus murinus
Cell and Tissue Research, 2019Co-Authors: Shota Takemi, Takafumi Sakai, Toru Tanaka, Shiomi Ojima, Ichiro SakataAbstract:Lysozyme is one of the most prominent antimicrobial peptides and has been identified from many mammalian species. However, this enzyme has not been studied in the order Insectivora, which includes the most primitive placental mammals. Here, we done the lysozyme cDNA from Suncus murinus (referred to as Suncus, its laboratory name) and compare the predicted amino acid sequence to those from other mammalian species. Quantitative PCR analysis revealed a relatively higher expression of this gene in the spleen and gastrointestinal tract of Suncus. The lysozyme-immunopositive (ip) cells were found mainly in the red pulp of the spleen and in the mucosa of the whole small intestine, including the follicle-associated epithelium and subepithelial dome of Peyer’s patches. The lysozyme-ip cells in the small intestine were mostly distributed in the intestinal crypt, although lysozyme-expressing cells were found not only in the crypt but also in the villi. On the other hand, only a few lysozyme-ip cells were found in the villi and some granules showing intense fluorescence were located toward the lumen. As reported for other mammals, Ki67-ip cells were localized in the crypt and did not co-localize with the lysozyme-ip cells. Moreover, fasting induced a decrease in the mRNA levels of lysozyme in the intestine of Suncus. In conclusion, we firstly identified the lysozyme mRNA sequence, clarified expression profile of lysozyme transcripts in Suncus and found a unique distribution of lysozyme-producing cells in the Suncus intestine.
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study of termination of postprandial gastric contractions in humans dogs and Suncus murinus role of motilin and ghrelin induced strong contraction
Acta Physiologica, 2018Co-Authors: Takashi Mikami, Takamichi Jogahara, Ichiro Sakata, Toru Tanaka, Shota Takemi, H O Diaztartera, Per M Hellstrom, E Mochiki, Sachiko Tsuda, Takafumi SakaiAbstract:Aim Stomach contractions show two types of specific patterns in many species, that is migrating motor contraction (MMC) and postprandial contractions (PPCs), in the fasting and fed states respectively. We found gastric PPCs terminated with migrating strong contractions in humans, dogs and Suncus. In this study, we reveal the detailed characteristics and physiological implications of these strong contractions of PPC. Methods Human, Suncus and canine gastric contractions were recorded with a motility-monitoring ingestible capsule and a strain-gauge force transducer. The response of motilin and ghrelin and its receptor antagonist on the contractions were studied by using free-moving Suncus. Results Strong gastric contractions were observed at the end of a PPC in human, dog and Suncus models, and we tentatively designated this contraction to be a postprandial giant contraction (PPGC). In the Suncus, the PPGC showed the same property as those of a phase III contraction of MMC (PIII-MMC) in the duration, motility index and response to motilin or ghrelin antagonist administration. Ghrelin antagonist administration in the latter half of the PPC (LH-PPC) attenuated gastric contraction prolonged the duration of occurrence of PPGC, as found in PII-MMC. Conclusion It is thought that the first half of the PPC changed to PII-MMC and then terminated with PIII-MMC, suggesting that PPC consists of a digestive phase (the first half of the PPC) and a discharge phase (LH-PPC) and that LH-PPC is coincident with MMC. In this study, we propose a new approach for the understanding of postprandial contractions.
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RESEARCH ARTICLE Motilin Stimulates Gastric Acid Secretion in Coordination with Ghrelin in Suncus murinus
2016Co-Authors: Chayon Goswami, Takafumi Sakai, Toru Tanaka, Yoshiaki Shimada, Makoto Yoshimura, Ichi Oda, Ichiro SakataAbstract:Motilin and ghrelin constitute a peptide family, and these hormones are important for the regulation of gastrointestinal motility. In this study, we examined the effect of motilin and ghrelin on gastric acid secretion in anesthetized Suncus (house musk shrew, Suncus muri-nus), a ghrelin- and motilin-producing mammal. We first established a gastric lumen-perfu-sion system in the Suncus and confirmed that intravenous (i.v.) administration of histamine (1 mg/kg body weight) stimulated acid secretion. Motilin (0.1, 1.0, and 10 μg/kg BW) stimu-lated the acid output in a dose-dependent manner in Suncus, whereas ghrelin (0.1, 1.0, and 10 μg/kg BW) alone did not induce acid output. Furthermore, in comparison with the vehicle administration, the co-administration of low-dose (1 μg/kg BW) motilin and ghrelin signifi-cantly stimulated gastric acid secretion, whereas either motilin (1 μg/kg BW) or ghrelin (1 μg/kg BW) alone did not significantly induce gastric acid secretion. This indicates an addi-tive role of ghrelin in motilin-induced gastric acid secretion. We then investigated the path-ways of motilin/motilin and ghrelin-stimulated acid secretion using receptor antagonists. Treatment with YM 022 (a CCK-B receptor antagonist) and atropine (a muscarinic acetyl-choline receptor antagonist) had no effect on motilin or motilin-ghrelin co-administration-induced acid output. In contrast, famotidine (a histamine H2 receptor antagonist) completely inhibited motilin-stimulated acid secretion and co-administration of motilin and ghrelin induced gastric acid output. This is the first report demonstrating that motilin stimulates gas-tric secretion in mammals. Our results also suggest that motilin and co-administration of motilin and ghrelin stimulate gastric acid secretion via the histamine-mediated pathway in Suncus
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The Role of the Vagus Nerve in the Migrating Motor Complex and Ghrelin- and Motilin-Induced Gastric Contraction in Suncus
2016Co-Authors: Yuki Miyano, Takamichi Jogahara, Sayaka Aizawa, Ichiro Sakata, Toru Tanaka, Kayuri Kuroda, Reiko Kurotani, Takafumi SakaiAbstract:The upper gastrointestinal (GI) tract undergoes a temporally coordinated cyclic motor pattern known as the migrating motor complex (MMC) in both dogs and humans during the fasted state. Feeding results in replacement of the MMC by a pattern of noncyclic, intermittent contractile activity termed as postprandial contractions. Although the MMC is known to be stimulated by motilin, recent studies have shown that ghrelin, which is from the same peptide family as motilin, is also involved in the regulation of the MMC. In the present study, we investigated the role of the vagus nerve on gastric motility using conscious Suncus—a motilin- and ghrelin-producing small animal. During the fasted state, cyclic MMC comprising phases I, II, and III was observed in both sham-operated and vagotomized Suncus; however, the duration and motility index (MI) of phase II was significantly decreased in vagotomized animals. Motilin infusion (50 ng?kg21?min21 for 10 min) during phase I had induced phase III–like contractions in both sham-operated and vagotomized animals. Ghrelin infusion (0.1, 0.3, 1, 3, or 10 mg?kg21?min21 for 10 min) enhanced the amplitude of phase II MMC in sham-operated animals, but not in vagotomized animals. After feeding, phase I was replaced by postprandial contractions, and motilin infusion (50 ng?kg21?min21 for 10 min) did not induce phase III–like contractions in sham-operated Suncus. However, in vagotomized Suncus, feeding did not evoke postprandial contractions, but exogenous motilin injection strongly induced phase III–like contractions, as noted during the phase I period. Thus, the results indicate that ghrelin stimulates phase II o
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motilin stimulates pepsinogen secretion in Suncus murinus
Biochemical and Biophysical Research Communications, 2015Co-Authors: Chayon Goswami, Takamichi Jogahara, Takafumi Sakai, Toru Tanaka, Ichiro SakataAbstract:Abstract Motilin and ghrelin are gastrointestinal hormones that stimulate the migrating motor complex (MMC) of gastrointestinal motility during the fasting state. In this study, we examined the effect of motilin and ghrelin on pepsinogen secretion in anesthetized Suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin-producing mammal. By using a gastric lumen-perfusion system, we found that the intravenous administration of carbachol and motilin stimulated pepsinogen secretion, the latter in a dose-dependent manner, whereas ghrelin had no effect. We then investigated the pathways of motilin-induced pepsinogen secretion using acetylcholine receptor antagonists. Treatment with atropine, a muscarinic acetylcholine receptor antagonist, completely inhibited both carbachol and motilin-induced pepsinogen secretion. Motilin-induced pepsinogen secretion was observed in the vagotomized Suncus. This is the first report demonstrating that motilin stimulates pepsinogen secretion, and suggest that this effect occurs through a cholinergic pathway in Suncus.
Norio Matsuki - One of the best experts on this subject based on the ideXlab platform.
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vasopressin induces emesis in Suncus murinus
Japanese Journal of Pharmacology, 2002Co-Authors: Yuji Ikegaya, Norio MatsukiAbstract:Abstract This paper reports that vasopressin is emetogenic in the house musk shrew Suncus murinus. Either intravenous or intracerebroventricular administration of vasopressin caused vomiting within a few minutes. The ED50 of intravenous vasopressin was as high as 4.67 μ g /kg, whereas intracerebroventricularly injected vasopressin was effective at a low dose of 20 ng /brain. The emetogenic target of vasopressin may therefore be present in the central nervous system. We propose the Suncus as a useful animal for investigation of vasopressin-mediated emesis, including motion sickness.
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antiemetic effects of morphine on motion and drug induced emesis in Suncus murinus
Biological & Pharmaceutical Bulletin, 1997Co-Authors: Shuichiro Kakimoto, Hiroshi Saito, Norio MatsukiAbstract:Emetic and antiemetic effects of morphine were investigated in Suncus murinus. Subcutaneous (up to 30 mg/kg) or intracerebroventricular administration (50 μg) of morphine failed to cause emesis. However, pretreatment with morphine (s.c.) prevented the emesis induced by nicotine (10 mg/kg, i.p.), copper sulfate (40 mg/kg, p.o.), cisplatin(20 mg/kg, i.p.) and motion stimulus. These results suggest that morphine has only antiemetic potency and may block a common mechanism for the emetic reflex of Suncus, because the antiemetic effects of the drug were exerted irrespective of the stimulus.
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the pharmacology of the emetic response to upper gastrointestinal tract stimulation in Suncus murinus
European Journal of Pharmacology, 1996Co-Authors: Paul L R Andrews, Hiroshi Saito, Yoshifumi Torii, Norio MatsukiAbstract:Abstract This paper is the first to describe aspects of the mechanics of retching in the insectivore Suncus murinus (house musk shrew) and in an animal of such a small size (∼ 50 g). In anaesthetised animals using the novel stimulus of mechanical stimulation of the upper gastrointestinal tract as the provocative stimulus the frequency of retching was found to be about 4 retches/s, a much higher frequency than in other species (dog, cat, ferret). These studies show that quantification of retching in Suncus cannot be undertaken using direct observation. The temporal pattern of the emetic response was characterised in conscious Suncus using motion (1 Hz, 5 min) and nicotine (20 mg/kg s.c.). The ultrapotent capsaicin analogue resiniferatoxin (100 μg/kg s.c.) was discovered to be highly emetic and comparative studies showed that nicotine and resiniferatoxin induced the most intense responses with episodes (retches and a vomit) occurring every 10–15 s. The retching response to mechanical stimulation in the anaesthetised Suncus was not blocked by a 5-HT 3 receptor antagonist (granisetron, 1–5 mg/kg s.c.), a tachykinin NK 1 receptor antagonist (CP-99,994 20 mg/kg s.c. dihydrochloride salt (9 +)-(2 S ,3 S )-3-(2-methoxybenzylamino)-2-phenylpiperidine) or morphine (2 mg/kg s.c.) but was blocked by the 5-HT 1A receptor agonist 8-hydroxy-2-(di- n -propylamino)tetralin (8-OH-DPAT 100 μg/kg s.c.). Suncus appears to be a suitable animal in which to study the pharmacology of the emetic response to mechanical stimulation of the gut. The results are discussed in the light of studies of the pharmacology of emesis in other species.
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the pharmacology of the emetic response to upper gastrointestinal tract stimulation in Suncus murinus
European Journal of Pharmacology, 1996Co-Authors: Paul L R Andrews, Hiroshi Saito, Yoshifumi Torii, Norio MatsukiAbstract:This paper is the first to describe aspects of the mechanics of retching in the insectivore Suncus murinus (house musk shrew) and in an animal of such a small size (approximately 50 g). In anaesthetised animals using the novel stimulus of mechanical stimulation of the upper gastrointestinal tract as the provocative stimulus the frequency of retching was found to be about 4 retches/s, a much higher frequency than in other species (dog, cat, ferret). These studies show that quantification of retching in Suncus cannot be undertaken using direct observation. The temporal pattern of the emetic response was characterised in conscious Suncus using motion (1 Hz, 5 min) and nicotine (20 mg/kg s.c.). The ultrapotent capsaicin analogue resiniferatoxin (100 micrograms/kg s.c.) was discovered to be highly emetic and comparative studies showed that nicotine and resiniferatoxin induced the most intense responses with episodes (retches and a vomit) occurring every 10-15 s. The retching response to mechanical stimulation in the anaesthetised Suncus was not blocked by a 5-HT3 receptor antagonist (granisetron, 1-5 mg/kg s.c.), a tachykinin NK1 receptor antagonist (CP-99,994 20 mg/kg s.c. dihydrochloride salt (9+) -(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine) or morphine (2 mg/kg s.c.) but was blocked by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT 100 micrograms/kg s.c.). Suncus appears to be a suitable animal in which to study the pharmacology of the emetic response to mechanical stimulation of the gut. The results are discussed in the light of studies of the pharmacology of emesis in other species.
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induction of emesis in Suncus murinus by pyrogallol a generator of free radicals
British Journal of Pharmacology, 1994Co-Authors: Yoshifumi Torii, Hiroshi Saito, Norio MatsukiAbstract:1. We investigated whether or not pyrogallol, a generator of free radicals, is emetogenic in Suncus murinus, the house musk shrew. Pyrogallol (i.p.) caused dose-dependent emesis in Suncus with an ED50 value of 77.3 mg kg-1. At a dose of 128 mg kg-1, all Suncus vomited with mean latency of 18.8 +/- 5.2 min and the number of vomiting episodes was 8.6 +/- 2.9. 2. The prophylactic effects of N-(2-mercaptopropionyl)-glycine (MPG), an antioxidant, and tropisetron, a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, were studied. Pyrogallol (128 mg kg-1, i.p.)-induced emesis was prevented by treatment with MPG (i.p.) or tropisetron (s.c.) with ID50 values of 149 mg kg-1 and 117 micrograms kg-1, respectively. 3. Pyrogallol-induced emesis was completely prevented by surgical abdominal vagotomy. 4. The present results indicate that pyrogallol-induced emesis is characteristically very similar to that caused by cisplatin and support the idea that generation of free radicals causes the release of peripheral 5-HT, which stimulates vagal afferent sensory nerves to cause emesis.
Toru Tanaka - One of the best experts on this subject based on the ideXlab platform.
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identification and characterization of an antimicrobial peptide lysozyme from Suncus murinus
Cell and Tissue Research, 2019Co-Authors: Shota Takemi, Takafumi Sakai, Toru Tanaka, Shiomi Ojima, Ichiro SakataAbstract:Lysozyme is one of the most prominent antimicrobial peptides and has been identified from many mammalian species. However, this enzyme has not been studied in the order Insectivora, which includes the most primitive placental mammals. Here, we done the lysozyme cDNA from Suncus murinus (referred to as Suncus, its laboratory name) and compare the predicted amino acid sequence to those from other mammalian species. Quantitative PCR analysis revealed a relatively higher expression of this gene in the spleen and gastrointestinal tract of Suncus. The lysozyme-immunopositive (ip) cells were found mainly in the red pulp of the spleen and in the mucosa of the whole small intestine, including the follicle-associated epithelium and subepithelial dome of Peyer’s patches. The lysozyme-ip cells in the small intestine were mostly distributed in the intestinal crypt, although lysozyme-expressing cells were found not only in the crypt but also in the villi. On the other hand, only a few lysozyme-ip cells were found in the villi and some granules showing intense fluorescence were located toward the lumen. As reported for other mammals, Ki67-ip cells were localized in the crypt and did not co-localize with the lysozyme-ip cells. Moreover, fasting induced a decrease in the mRNA levels of lysozyme in the intestine of Suncus. In conclusion, we firstly identified the lysozyme mRNA sequence, clarified expression profile of lysozyme transcripts in Suncus and found a unique distribution of lysozyme-producing cells in the Suncus intestine.
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study of termination of postprandial gastric contractions in humans dogs and Suncus murinus role of motilin and ghrelin induced strong contraction
Acta Physiologica, 2018Co-Authors: Takashi Mikami, Takamichi Jogahara, Ichiro Sakata, Toru Tanaka, Shota Takemi, H O Diaztartera, Per M Hellstrom, E Mochiki, Sachiko Tsuda, Takafumi SakaiAbstract:Aim Stomach contractions show two types of specific patterns in many species, that is migrating motor contraction (MMC) and postprandial contractions (PPCs), in the fasting and fed states respectively. We found gastric PPCs terminated with migrating strong contractions in humans, dogs and Suncus. In this study, we reveal the detailed characteristics and physiological implications of these strong contractions of PPC. Methods Human, Suncus and canine gastric contractions were recorded with a motility-monitoring ingestible capsule and a strain-gauge force transducer. The response of motilin and ghrelin and its receptor antagonist on the contractions were studied by using free-moving Suncus. Results Strong gastric contractions were observed at the end of a PPC in human, dog and Suncus models, and we tentatively designated this contraction to be a postprandial giant contraction (PPGC). In the Suncus, the PPGC showed the same property as those of a phase III contraction of MMC (PIII-MMC) in the duration, motility index and response to motilin or ghrelin antagonist administration. Ghrelin antagonist administration in the latter half of the PPC (LH-PPC) attenuated gastric contraction prolonged the duration of occurrence of PPGC, as found in PII-MMC. Conclusion It is thought that the first half of the PPC changed to PII-MMC and then terminated with PIII-MMC, suggesting that PPC consists of a digestive phase (the first half of the PPC) and a discharge phase (LH-PPC) and that LH-PPC is coincident with MMC. In this study, we propose a new approach for the understanding of postprandial contractions.
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RESEARCH ARTICLE Motilin Stimulates Gastric Acid Secretion in Coordination with Ghrelin in Suncus murinus
2016Co-Authors: Chayon Goswami, Takafumi Sakai, Toru Tanaka, Yoshiaki Shimada, Makoto Yoshimura, Ichi Oda, Ichiro SakataAbstract:Motilin and ghrelin constitute a peptide family, and these hormones are important for the regulation of gastrointestinal motility. In this study, we examined the effect of motilin and ghrelin on gastric acid secretion in anesthetized Suncus (house musk shrew, Suncus muri-nus), a ghrelin- and motilin-producing mammal. We first established a gastric lumen-perfu-sion system in the Suncus and confirmed that intravenous (i.v.) administration of histamine (1 mg/kg body weight) stimulated acid secretion. Motilin (0.1, 1.0, and 10 μg/kg BW) stimu-lated the acid output in a dose-dependent manner in Suncus, whereas ghrelin (0.1, 1.0, and 10 μg/kg BW) alone did not induce acid output. Furthermore, in comparison with the vehicle administration, the co-administration of low-dose (1 μg/kg BW) motilin and ghrelin signifi-cantly stimulated gastric acid secretion, whereas either motilin (1 μg/kg BW) or ghrelin (1 μg/kg BW) alone did not significantly induce gastric acid secretion. This indicates an addi-tive role of ghrelin in motilin-induced gastric acid secretion. We then investigated the path-ways of motilin/motilin and ghrelin-stimulated acid secretion using receptor antagonists. Treatment with YM 022 (a CCK-B receptor antagonist) and atropine (a muscarinic acetyl-choline receptor antagonist) had no effect on motilin or motilin-ghrelin co-administration-induced acid output. In contrast, famotidine (a histamine H2 receptor antagonist) completely inhibited motilin-stimulated acid secretion and co-administration of motilin and ghrelin induced gastric acid output. This is the first report demonstrating that motilin stimulates gas-tric secretion in mammals. Our results also suggest that motilin and co-administration of motilin and ghrelin stimulate gastric acid secretion via the histamine-mediated pathway in Suncus
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The Role of the Vagus Nerve in the Migrating Motor Complex and Ghrelin- and Motilin-Induced Gastric Contraction in Suncus
2016Co-Authors: Yuki Miyano, Takamichi Jogahara, Sayaka Aizawa, Ichiro Sakata, Toru Tanaka, Kayuri Kuroda, Reiko Kurotani, Takafumi SakaiAbstract:The upper gastrointestinal (GI) tract undergoes a temporally coordinated cyclic motor pattern known as the migrating motor complex (MMC) in both dogs and humans during the fasted state. Feeding results in replacement of the MMC by a pattern of noncyclic, intermittent contractile activity termed as postprandial contractions. Although the MMC is known to be stimulated by motilin, recent studies have shown that ghrelin, which is from the same peptide family as motilin, is also involved in the regulation of the MMC. In the present study, we investigated the role of the vagus nerve on gastric motility using conscious Suncus—a motilin- and ghrelin-producing small animal. During the fasted state, cyclic MMC comprising phases I, II, and III was observed in both sham-operated and vagotomized Suncus; however, the duration and motility index (MI) of phase II was significantly decreased in vagotomized animals. Motilin infusion (50 ng?kg21?min21 for 10 min) during phase I had induced phase III–like contractions in both sham-operated and vagotomized animals. Ghrelin infusion (0.1, 0.3, 1, 3, or 10 mg?kg21?min21 for 10 min) enhanced the amplitude of phase II MMC in sham-operated animals, but not in vagotomized animals. After feeding, phase I was replaced by postprandial contractions, and motilin infusion (50 ng?kg21?min21 for 10 min) did not induce phase III–like contractions in sham-operated Suncus. However, in vagotomized Suncus, feeding did not evoke postprandial contractions, but exogenous motilin injection strongly induced phase III–like contractions, as noted during the phase I period. Thus, the results indicate that ghrelin stimulates phase II o
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motilin stimulates pepsinogen secretion in Suncus murinus
Biochemical and Biophysical Research Communications, 2015Co-Authors: Chayon Goswami, Takamichi Jogahara, Takafumi Sakai, Toru Tanaka, Ichiro SakataAbstract:Abstract Motilin and ghrelin are gastrointestinal hormones that stimulate the migrating motor complex (MMC) of gastrointestinal motility during the fasting state. In this study, we examined the effect of motilin and ghrelin on pepsinogen secretion in anesthetized Suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin-producing mammal. By using a gastric lumen-perfusion system, we found that the intravenous administration of carbachol and motilin stimulated pepsinogen secretion, the latter in a dose-dependent manner, whereas ghrelin had no effect. We then investigated the pathways of motilin-induced pepsinogen secretion using acetylcholine receptor antagonists. Treatment with atropine, a muscarinic acetylcholine receptor antagonist, completely inhibited both carbachol and motilin-induced pepsinogen secretion. Motilin-induced pepsinogen secretion was observed in the vagotomized Suncus. This is the first report demonstrating that motilin stimulates pepsinogen secretion, and suggest that this effect occurs through a cholinergic pathway in Suncus.
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study of termination of postprandial gastric contractions in humans dogs and Suncus murinus role of motilin and ghrelin induced strong contraction
Acta Physiologica, 2018Co-Authors: Takashi Mikami, Takamichi Jogahara, Ichiro Sakata, Toru Tanaka, Shota Takemi, H O Diaztartera, Per M Hellstrom, E Mochiki, Sachiko Tsuda, Takafumi SakaiAbstract:Aim Stomach contractions show two types of specific patterns in many species, that is migrating motor contraction (MMC) and postprandial contractions (PPCs), in the fasting and fed states respectively. We found gastric PPCs terminated with migrating strong contractions in humans, dogs and Suncus. In this study, we reveal the detailed characteristics and physiological implications of these strong contractions of PPC. Methods Human, Suncus and canine gastric contractions were recorded with a motility-monitoring ingestible capsule and a strain-gauge force transducer. The response of motilin and ghrelin and its receptor antagonist on the contractions were studied by using free-moving Suncus. Results Strong gastric contractions were observed at the end of a PPC in human, dog and Suncus models, and we tentatively designated this contraction to be a postprandial giant contraction (PPGC). In the Suncus, the PPGC showed the same property as those of a phase III contraction of MMC (PIII-MMC) in the duration, motility index and response to motilin or ghrelin antagonist administration. Ghrelin antagonist administration in the latter half of the PPC (LH-PPC) attenuated gastric contraction prolonged the duration of occurrence of PPGC, as found in PII-MMC. Conclusion It is thought that the first half of the PPC changed to PII-MMC and then terminated with PIII-MMC, suggesting that PPC consists of a digestive phase (the first half of the PPC) and a discharge phase (LH-PPC) and that LH-PPC is coincident with MMC. In this study, we propose a new approach for the understanding of postprandial contractions.
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identification of the sexually dimorphic gastrin releasing peptide system in the lumbosacral spinal cord that controls male reproductive function in the mouse and asian house musk shrew Suncus murinus
The Journal of Comparative Neurology, 2017Co-Authors: Kei Tamura, Takamichi Jogahara, Yasuhisa Kobayashi, Asuka Hirooka, Keiko Takanami, Tatsuya Sakamoto, Hirotaka SakamotoAbstract:Several regions of the brain and spinal cord control male reproductive function. We previously demonstrated that the gastrin-releasing peptide (GRP) system, located in the lumbosacral spinal cord of rats, controls spinal centers to promote penile reflexes during male copulatory behavior. However, little information exists on the male-specific spinal GRP system in animals other than rats. The objective of this study was to examine the functional generality of the spinal GRP system in mammals using the Asian house musk shrew (Suncus murinus; Suncus named as the laboratory strain), a specialized placental mammal model. Mice are also used for a representative model of small laboratory animals. We first isolated complementary DNA encoding GRP in Suncus. Phylogenetic analysis revealed that Suncus preproGRP was clustered to an independent branch. Reverse transcription-PCR showed that GRP and its receptor mRNAs were both expressed in the lumbar spinal cord of Suncus and mice. Immunohistochemistry for GRP demonstrated that the sexually dimorphic GRP system and male-specific expression/distribution patterns of GRP in the lumbosacral spinal cord in Suncus are similar to those of mice. In Suncus, we further found that most GRP-expressing neurons in males also express androgen receptors, suggesting that this male-dominant system in Suncus is also androgen-dependent. Taken together, these results indicate that the sexually dimorphic spinal GRP system exists not only in mice but also in Suncus, suggesting that this system is a conserved property in mammals. This article is protected by copyright. All rights reserved.
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comparative anatomy of gastrin releasing peptide pathways in the trigeminal sensory system of mouse and the asian house musk shrew Suncus murinus
Acta Histochemica Et Cytochemica, 2016Co-Authors: Keiko Takanami, Takamichi Jogahara, Kei Tamura, Tatsuya Sakamoto, Senichi Oda, Kaihei Inoue, Hiroki Mukai, Mitsuhiro Kawata, Hirotaka SakamotoAbstract:Gastrin-releasing peptide (GRP) has recently been identified as an itch-signaling molecule in the primary afferents and spinal cord of rodents. However, little information exists on the expression and localization of GRP in the trigeminal somatosensory system other than in rats. We examined the generality of the trigeminal GRP system in mammals using two distinct species, Suncus as a model of specialized placental mammals known to have a well-developed trigeminal sensory system and mice as a representative small laboratory animal. We first analyzed the gross morphology of the trigeminal somatosensory system in Suncus to provide a brainstem atlas on which to map GRP distribution. Immunohistochemical analyses showed that 8% of trigeminal ganglion neurons in Suncus and 6% in mice expressed GRP. Expression was restricted to cells with smaller somata. The GRP-containing fibers were densely distributed in the superficial layers of the caudal part of the trigeminal spinal nucleus (Vc) but rare in the rostral parts, both in Suncus and mice. Expression of GRP receptor mRNA and protein was also detected in the Vc of Suncus. Taken together, these results suggest that the trigeminal GRP system mediating itch sensation is conserved in mammals.
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The Role of the Vagus Nerve in the Migrating Motor Complex and Ghrelin- and Motilin-Induced Gastric Contraction in Suncus
2016Co-Authors: Yuki Miyano, Takamichi Jogahara, Sayaka Aizawa, Ichiro Sakata, Toru Tanaka, Kayuri Kuroda, Reiko Kurotani, Takafumi SakaiAbstract:The upper gastrointestinal (GI) tract undergoes a temporally coordinated cyclic motor pattern known as the migrating motor complex (MMC) in both dogs and humans during the fasted state. Feeding results in replacement of the MMC by a pattern of noncyclic, intermittent contractile activity termed as postprandial contractions. Although the MMC is known to be stimulated by motilin, recent studies have shown that ghrelin, which is from the same peptide family as motilin, is also involved in the regulation of the MMC. In the present study, we investigated the role of the vagus nerve on gastric motility using conscious Suncus—a motilin- and ghrelin-producing small animal. During the fasted state, cyclic MMC comprising phases I, II, and III was observed in both sham-operated and vagotomized Suncus; however, the duration and motility index (MI) of phase II was significantly decreased in vagotomized animals. Motilin infusion (50 ng?kg21?min21 for 10 min) during phase I had induced phase III–like contractions in both sham-operated and vagotomized animals. Ghrelin infusion (0.1, 0.3, 1, 3, or 10 mg?kg21?min21 for 10 min) enhanced the amplitude of phase II MMC in sham-operated animals, but not in vagotomized animals. After feeding, phase I was replaced by postprandial contractions, and motilin infusion (50 ng?kg21?min21 for 10 min) did not induce phase III–like contractions in sham-operated Suncus. However, in vagotomized Suncus, feeding did not evoke postprandial contractions, but exogenous motilin injection strongly induced phase III–like contractions, as noted during the phase I period. Thus, the results indicate that ghrelin stimulates phase II o
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motilin stimulates pepsinogen secretion in Suncus murinus
Biochemical and Biophysical Research Communications, 2015Co-Authors: Chayon Goswami, Takamichi Jogahara, Takafumi Sakai, Toru Tanaka, Ichiro SakataAbstract:Abstract Motilin and ghrelin are gastrointestinal hormones that stimulate the migrating motor complex (MMC) of gastrointestinal motility during the fasting state. In this study, we examined the effect of motilin and ghrelin on pepsinogen secretion in anesthetized Suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin-producing mammal. By using a gastric lumen-perfusion system, we found that the intravenous administration of carbachol and motilin stimulated pepsinogen secretion, the latter in a dose-dependent manner, whereas ghrelin had no effect. We then investigated the pathways of motilin-induced pepsinogen secretion using acetylcholine receptor antagonists. Treatment with atropine, a muscarinic acetylcholine receptor antagonist, completely inhibited both carbachol and motilin-induced pepsinogen secretion. Motilin-induced pepsinogen secretion was observed in the vagotomized Suncus. This is the first report demonstrating that motilin stimulates pepsinogen secretion, and suggest that this effect occurs through a cholinergic pathway in Suncus.
