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In this study, we examined the effect of motilin and ghrelin on gastric acid secretion in anesthetized suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin-producing mammal. We first established a gastric lumen-perfusion system in the suncus and confirmed that intravenous (i.v.) administration of histamine (1 mg/kg BW) stimulated acid secretion. Motilin (0.1, 1.0, and 10 μg/kg BW) stimulated 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 significantly 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 additive role of ghrelin in motilin-induced gastric acid secretion. We then investigated the pathways of motilin/motilin and ghrelin-stimulated acid secretion using receptor antagonists. Treatment with YM 022 (a CCK-B receptor antagonist) and atropine (a muscarinic acetylcholine 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 gastric secretion in mammals. By using the above mentioned gastric lumen-perfusion system, we also found that the intravenous administration of carbachol and motilin (0.1, 1.0, and 10 μg/kg BW) 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 also observed in the vagotomized suncus. Our results suggest that motilin stimulates gastric acid secretion via the histamine-mediated pathway and also stimulates pepsinogen secretion through a cholinergic pathway in suncus.", "subitem_description_type": "Abstract"}]}, "item_113_description_24": {"attribute_name": "目次", "attribute_value_mlt": [{"subitem_description": "ABSTRACT I\nACKNOWLEDGEMENTS III\nTABLE OF CONTENTS V\nLIST OF FIGURES IX\nChapter 1: General Introduction and Objectives 1\n1.1. Research background 1\n1.1.1. Gastric acid secretion and its role in gastric acid secretion 1\n1.1.2. Pepsinogen secretion and its role in gastric acid secretion 1\n1.1.3. Motilin 2\n1.1.4. Ghrelin 2\n1.1.5. Similar properties between motilin and ghrelin 3\n1.1.6. House musk shrew (Suncus murinus) 4\n1.2. Hypothesis 5\n1.3. General objectives 5\nChapter 2: Motilin stimulates gastric acid secretion in co-ordination with ghrelin in Suncus murinus 6\n2.1. Introduction 6\n2.1.1. Gastric acid secretion mechanism 6\n2.1.2. Motilin and ghrelin, and their functions in relation to gastric acid secretion 6\n2.1.3. Advantages of suncus for studying gastrointestinal physiology including gastric acid experiment 7\n2.2. Materials and Methods 9\n2.2.1. Animals 9\n2.2.2. Drugs 9\n2.2.3. Determination of gastric acid output by an intragastric perfusion experimental system 10\n2.2.4. Measurement of pH and amount of gastric acid 11\n2.2.5. Experimental protocols 11\n2.2.6. Statistical analyses 12\n2.3. Results 13\n2.3.1. Effect of ghrelin, motilin, and co-administration of motilin and ghrelin on gastric acid secretion 13\n2.3.2. Effect of famotidine on motilin, and co-administration of motilin and ghrelin-stimulated gastric acid secretion 14\n2.3.3. Effect of YM 022 on gastric acid secretion stimulated by motilin, and co-administration of motilin and ghrelin 15\n2.3.4. Effect of atropine on motilin, and co-administration of motilin and ghrelin-stimulated gastric acid secretion 15\n2.4. Discussion 17\n2.4.1. Suncus for gastric acid secretion study 17\n2.4.2. Motilin but not ghrelin stimulate gastric acid secretion 17\n2.4.3. Physiological importance of motilin-induced gastric acid secretion 18\n2.4.4. Regulatory mechanism of motilin-induced gastric acid secretion 19\n2.5. Summary 21\nChapter 3: Motilin stimulates pepsinogen secretion in Suncus murinus 22\n3.1. Introduction 22\n3.1.1. Regulatory mechanism of pepsinogen secretion 22\n3.1.2. Motilin and ghrelin, and their functions in gastrointestinal tract 23\n3.1.3. Advantages of suncus as an experimental animal for pepsinogen secretion study 23\n3.1.4. Gastric contraction and pepsinogen secretion 24\n3.2. Materials and Methods 25\n3.2.1. Animals 25\n3.2.2. Drugs 25\n3.2.3. Determination of pepsin output using an intragastric perfusion experimental system 25\n3.2.4. Vagotomy 26\n3.2.5. Pepsin measurement 27\n3.2.6. Experimental protocols 27\n3.2.7. Statistical analyses 28\n3.3. Results 29\n3.3.1. Establishment of a perfusion system for pepsinogen measurement in suncus 29\n3.3.2. Effects of motilin on pepsinogen secretion 29\n3.3.3. Effects of ghrelin on pepsinogen secretion 29\n3.3.4. Effect of atropine on motilin-induced pepsinogen secretion 30\n3.3.5. Effect of vagotomy on motilin-induced pepsinogen secretion 30\n3.3.6. Effect of motilin and histamine on both pH and pepsinogen secretion 31\n3.3.7. Effect of co-administration of motilin and ghrelin on pepsinogen secretion 31\n3.4. Discussion 32\n3.4.1. Suncus as a suitable model animal for pepsinogen secretion experiments 32\n3.4.2. Motilin-induced pepsinogen secretion and its physiological importance 32\n3.4.3. Motilin but not ghrelin stimulates pepsinogen secretion through cholinergic pathway 34\n3.5. Summary 35\nCONCLUSIONS 36\nABBREVIATIONS 37\nREFERENCES 38\nFIGURES 49", "subitem_description_type": "Other"}]}, "item_113_description_25": {"attribute_name": "注記", "attribute_value_mlt": [{"subitem_description": "指導教員 : 坂井貴文", "subitem_description_type": "Other"}]}, "item_113_description_33": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"subitem_description": "text", "subitem_description_type": "Other"}]}, "item_113_description_34": {"attribute_name": "フォーマット", "attribute_value_mlt": [{"subitem_description": "application/pdf", "subitem_description_type": "Other"}]}, "item_113_dissertation_number_19": {"attribute_name": "学位授与番号", "attribute_value_mlt": [{"subitem_dissertationnumber": "甲第990号"}]}, "item_113_identifier_registration": {"attribute_name": "ID登録", "attribute_value_mlt": [{"subitem_identifier_reg_text": "10.24561/00010369", "subitem_identifier_reg_type": "JaLC"}]}, "item_113_publisher_11": {"attribute_name": "出版者名", "attribute_value_mlt": [{"subitem_publisher": "埼玉大学大学院理工学研究科"}]}, "item_113_publisher_12": {"attribute_name": "出版者名(別言語)", "attribute_value_mlt": [{"subitem_publisher": "Graduate School of Science and Engineering, Saitama University"}]}, "item_113_record_name_8": {"attribute_name": "書誌", "attribute_value_mlt": [{"subitem_record_name": "博士論文(埼玉大学大学院理工学研究科(博士後期課程))"}]}, "item_113_text_31": {"attribute_name": "版", "attribute_value_mlt": [{"subitem_text_value": "[出版社版]"}]}, "item_113_text_36": {"attribute_name": "アイテムID", "attribute_value_mlt": [{"subitem_text_value": "GD0000716"}]}, "item_113_text_4": {"attribute_name": "著者 所属", "attribute_value_mlt": [{"subitem_text_value": "埼玉大学大学院理工学研究科(博士後期課程)理工学専攻"}]}, "item_113_text_5": {"attribute_name": "著者 所属(別言語)", "attribute_value_mlt": [{"subitem_text_value": "Graduate School of Science and Engineering, Saitama University"}]}, "item_113_version_type_32": {"attribute_name": "著者版フラグ", "attribute_value_mlt": [{"subitem_version_resource": "http://purl.org/coar/version/c_970fb48d4fbd8a85", "subitem_version_type": "VoR"}]}, "item_access_right": {"attribute_name": "アクセス権", "attribute_value_mlt": [{"subitem_access_right": "open access", "subitem_access_right_uri": "http://purl.org/coar/access_right/c_abf2"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "CHAYON, GOSWAMI", "creatorNameLang": "en"}, {"creatorName": "チャヨン, グッサミ", "creatorNameLang": "ja-Kana"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2018-01-23"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "GD0000716.pdf", "filesize": [{"value": "8.8 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 8800000.0, "url": {"label": "GD0000716.pdf", "objectType": "fulltext", "url": "https://sucra.repo.nii.ac.jp/record/10375/files/GD0000716.pdf"}, "version_id": "5223fa96-e187-4fa7-86dd-7673e73e5380"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "doctoral thesis", "resourceuri": "http://purl.org/coar/resource_type/c_db06"}]}, "item_title": "The regulatory mechanism of motilin induced gastric acid and pepsinogen secretion in Suncus murinus", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "The regulatory mechanism of motilin induced gastric acid and pepsinogen secretion in Suncus murinus", "subitem_title_language": "en"}]}, "item_type_id": "113", "owner": "15", "path": ["507"], "permalink_uri": "https://doi.org/10.24561/00010369", "pubdate": {"attribute_name": "PubDate", "attribute_value": "2016-08-09"}, "publish_date": "2016-08-09", "publish_status": "0", "recid": "10375", "relation": {}, "relation_version_is_last": true, "title": ["The regulatory mechanism of motilin induced gastric acid and pepsinogen secretion in Suncus murinus"], "weko_shared_id": -1}
The regulatory mechanism of motilin induced gastric acid and pepsinogen secretion in Suncus murinus
https://doi.org/10.24561/00010369
https://doi.org/10.24561/00010369c1bf630e-3cc2-4b2a-b64c-b19a04dbfe25
名前 / ファイル | ライセンス | アクション |
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GD0000716.pdf (8.8 MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
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公開日 | 2016-08-09 | |||||||||
タイトル | ||||||||||
言語 | en | |||||||||
タイトル | The regulatory mechanism of motilin induced gastric acid and pepsinogen secretion in Suncus murinus | |||||||||
言語 | ||||||||||
言語 | eng | |||||||||
資源タイプ | ||||||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||
資源タイプ | doctoral thesis | |||||||||
ID登録 | ||||||||||
ID登録 | 10.24561/00010369 | |||||||||
ID登録タイプ | JaLC | |||||||||
アクセス権 | ||||||||||
アクセス権 | open access | |||||||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||
タイトル(別言語) | ||||||||||
その他のタイトル | スンクスにおけるモチリン誘導性胃酸及びペプシノーゲン分泌調節機構 | |||||||||
著者 |
CHAYON, GOSWAMI
× CHAYON, GOSWAMI
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著者 所属 | ||||||||||
埼玉大学大学院理工学研究科(博士後期課程)理工学専攻 | ||||||||||
著者 所属(別言語) | ||||||||||
Graduate School of Science and Engineering, Saitama University | ||||||||||
書誌 | ||||||||||
収録物名 | 博士論文(埼玉大学大学院理工学研究科(博士後期課程)) | |||||||||
書誌情報 |
発行日 2015 |
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出版者名 | ||||||||||
出版者 | 埼玉大学大学院理工学研究科 | |||||||||
出版者名(別言語) | ||||||||||
出版者 | Graduate School of Science and Engineering, Saitama University | |||||||||
形態 | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | x, 66 p. | |||||||||
学位授与番号 | ||||||||||
学位授与番号 | 甲第990号 | |||||||||
学位授与年月日 | ||||||||||
学位授与年月日 | 2015-09-18 | |||||||||
学位名 | ||||||||||
学位名 | 博士(学術) | |||||||||
学位授与機関 | ||||||||||
学位授与機関識別子Scheme | kakenhi | |||||||||
学位授与機関識別子 | 12401 | |||||||||
学位授与機関名 | 埼玉大学 | |||||||||
抄録 | ||||||||||
内容記述タイプ | Abstract | |||||||||
内容記述 | 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 murinus), a ghrelin- and motilin-producing mammal. We first established a gastric lumen-perfusion system in the suncus and confirmed that intravenous (i.v.) administration of histamine (1 mg/kg BW) stimulated acid secretion. Motilin (0.1, 1.0, and 10 μg/kg BW) stimulated 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 significantly 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 additive role of ghrelin in motilin-induced gastric acid secretion. We then investigated the pathways of motilin/motilin and ghrelin-stimulated acid secretion using receptor antagonists. Treatment with YM 022 (a CCK-B receptor antagonist) and atropine (a muscarinic acetylcholine 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 gastric secretion in mammals. By using the above mentioned gastric lumen-perfusion system, we also found that the intravenous administration of carbachol and motilin (0.1, 1.0, and 10 μg/kg BW) 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 also observed in the vagotomized suncus. Our results suggest that motilin stimulates gastric acid secretion via the histamine-mediated pathway and also stimulates pepsinogen secretion through a cholinergic pathway in suncus. | |||||||||
目次 | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | ABSTRACT I ACKNOWLEDGEMENTS III TABLE OF CONTENTS V LIST OF FIGURES IX Chapter 1: General Introduction and Objectives 1 1.1. Research background 1 1.1.1. Gastric acid secretion and its role in gastric acid secretion 1 1.1.2. Pepsinogen secretion and its role in gastric acid secretion 1 1.1.3. Motilin 2 1.1.4. Ghrelin 2 1.1.5. Similar properties between motilin and ghrelin 3 1.1.6. House musk shrew (Suncus murinus) 4 1.2. Hypothesis 5 1.3. General objectives 5 Chapter 2: Motilin stimulates gastric acid secretion in co-ordination with ghrelin in Suncus murinus 6 2.1. Introduction 6 2.1.1. Gastric acid secretion mechanism 6 2.1.2. Motilin and ghrelin, and their functions in relation to gastric acid secretion 6 2.1.3. Advantages of suncus for studying gastrointestinal physiology including gastric acid experiment 7 2.2. Materials and Methods 9 2.2.1. Animals 9 2.2.2. Drugs 9 2.2.3. Determination of gastric acid output by an intragastric perfusion experimental system 10 2.2.4. Measurement of pH and amount of gastric acid 11 2.2.5. Experimental protocols 11 2.2.6. Statistical analyses 12 2.3. Results 13 2.3.1. Effect of ghrelin, motilin, and co-administration of motilin and ghrelin on gastric acid secretion 13 2.3.2. Effect of famotidine on motilin, and co-administration of motilin and ghrelin-stimulated gastric acid secretion 14 2.3.3. Effect of YM 022 on gastric acid secretion stimulated by motilin, and co-administration of motilin and ghrelin 15 2.3.4. Effect of atropine on motilin, and co-administration of motilin and ghrelin-stimulated gastric acid secretion 15 2.4. Discussion 17 2.4.1. Suncus for gastric acid secretion study 17 2.4.2. Motilin but not ghrelin stimulate gastric acid secretion 17 2.4.3. Physiological importance of motilin-induced gastric acid secretion 18 2.4.4. Regulatory mechanism of motilin-induced gastric acid secretion 19 2.5. Summary 21 Chapter 3: Motilin stimulates pepsinogen secretion in Suncus murinus 22 3.1. Introduction 22 3.1.1. Regulatory mechanism of pepsinogen secretion 22 3.1.2. Motilin and ghrelin, and their functions in gastrointestinal tract 23 3.1.3. Advantages of suncus as an experimental animal for pepsinogen secretion study 23 3.1.4. Gastric contraction and pepsinogen secretion 24 3.2. Materials and Methods 25 3.2.1. Animals 25 3.2.2. Drugs 25 3.2.3. Determination of pepsin output using an intragastric perfusion experimental system 25 3.2.4. Vagotomy 26 3.2.5. Pepsin measurement 27 3.2.6. Experimental protocols 27 3.2.7. Statistical analyses 28 3.3. Results 29 3.3.1. Establishment of a perfusion system for pepsinogen measurement in suncus 29 3.3.2. Effects of motilin on pepsinogen secretion 29 3.3.3. Effects of ghrelin on pepsinogen secretion 29 3.3.4. Effect of atropine on motilin-induced pepsinogen secretion 30 3.3.5. Effect of vagotomy on motilin-induced pepsinogen secretion 30 3.3.6. Effect of motilin and histamine on both pH and pepsinogen secretion 31 3.3.7. Effect of co-administration of motilin and ghrelin on pepsinogen secretion 31 3.4. Discussion 32 3.4.1. Suncus as a suitable model animal for pepsinogen secretion experiments 32 3.4.2. Motilin-induced pepsinogen secretion and its physiological importance 32 3.4.3. Motilin but not ghrelin stimulates pepsinogen secretion through cholinergic pathway 34 3.5. Summary 35 CONCLUSIONS 36 ABBREVIATIONS 37 REFERENCES 38 FIGURES 49 |
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注記 | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | 指導教員 : 坂井貴文 | |||||||||
版 | ||||||||||
[出版社版] | ||||||||||
著者版フラグ | ||||||||||
出版タイプ | VoR | |||||||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||
資源タイプ | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | text | |||||||||
フォーマット | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | application/pdf | |||||||||
作成日 | ||||||||||
日付 | 2016-08-09 | |||||||||
日付タイプ | Created | |||||||||
アイテムID | ||||||||||
GD0000716 |