生理学研究所年報 第28巻
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19.第3回唾液腺機能からの生理機能研究・その戦略的展開
(第3回ニールスステンセン記念国際唾液腺シンポジウム,
第36回生理研国際シンポジウムと合同開催)

2006年10月20日−10月23日
代表・世話人:村上政隆(自然科学研究機構生理学研究所統合バイオサイエンスセンター)
所内対応者:同上

O. Opening Lecture

(0)
Stensen and early history of glands and exocrine secretion.
Alessandro Riva (Cagliari University)

A. Diagnostics using saliva and Proteomics of saliva.

(1)
Clinical examination using saliva: Influence of fluid secretion on the concentration of substrate in saliva:
How to overcome the problem for in vivo application.
Masataka Murakami (National Institute for Physiological Sciences, NINS), Naoki Shinozuka (SapporoIDL)
(2)
Extraoral functions of salivary proteins.
Anders Bennick (Toronto University)
(3)
Human salivary proteins- A fascinating complex of polymorphic and polyfunctional proteins.
Josie A Beeley (Glasgow University)
P1:
A proteomic study of saliva from celiac patients.
Tiziana Cabras (Cagliari University)
P2:
Salivary acidic proline-rich proteins in preterm newborns.
Rosanna Inzitari (Catholic University of Rome)
P3:
Oxidative modification of serum albumin via paracellular route of rat submandibular gland.
Tomoya Hayashi (Meiji University of Oriental Medicine)
P4:
A preliminary study on salivary protein expression in diabetic patients.
Marco Piludu (Cagliari University)
P5:
Clinical examination using saliva: an in vivo application to human adults.
Naoki Shinozuka (Sapporo IDL)
(4)
How the technique works and how the researcher can take a profit from the MS strategies.
Massimo Castagnola (Catholic University of Rome)
(5)
Salivary glands and saliva composition: a proteomic approach.
Francisco ML Amado (Aveiro University)
(6)
Salivary peptides as potential substrates of type2 transglutaminase.
Irene Messana (Cagliari University)
(7)
Pre-secretory Post-translational modifications common to different families of human salivary proteins.
Massimo Castagnola (Catholic University of Rome)
(8)
Tissue kallikrein mK13 is a candidate of the processing enzyme for pro-IL-1b in the mouse submandibular gland.
Chenjuan Yao (Tokushima University Graduate School)
P6:
Protein content comparison of mouse submandibular and parotid salivary glands.
Rui Vitorino (Aveiro University)
P7:
Characterization of different proline-rich peptides from pig parotid glands.
Chiara Fanali (Catholic University of Rome)
P8:
Tyrosine sulfation of Histatin 1. A post-translational modification specific of submandibular glands.
Joanna Anton Monteiro, Massimo Castagnola (Catholic University of Rome)
P9:
Different roles of salivary mucins in viscosity and spinnbarkeit of human saliva.
Hiroko Inoue (Kyushu Dental College)
P10:
MALDI based Mass Imaging revealed abnormal distribution of phospholipids in cancer.
Takahiro Hayasaka, Mitsutoshi Setoh (Okazaki Institute for Integrative Bioscience, NINS)

B. Therapeutics by modulation of salivary gland.

(9)
Clinical applications of gene transfer to salivary glands.
Bruce Baum (National Institute of Dental and Craniofacial Research, NIH, DHHS)
(10)
Morphogenesis and cleft formation of salivary gland epithelia: Exploration of new functional regulators.
Takayoshi Sakai (Osaka University Graduate School of Dentistry)
P11:
A novel role of RbAp48 for tissue-specific apoptosis in the salivary glands depending on estrogen deficiency.
Naozumi Ishimaru (Institute of Health Biosciences, Tokushima University Graduate School)
P12:
Ionomycin inhibit the soluble protein transport between ER and Golgi.
Masatake Asano (Nihon University School of Dentistry)
P13:
Investigation on the influences of Chinese herbs on salivary secretion in rat submandibular gland.
Wei Muxin (Nanjing Medical University)
P14:
Possible involvement of clusterin in the regeneration process of rat submandibular gland.
Hideaki Kagami (Institute of Medical Sciences, University of Tokyo)
P15:
Effect of Dan Di Qiong Yu granule on salivary gland of Sjogren syndrome mice.
Wei Muxin (Nanjing Medical University)

C. Neural control of salivary secretion in response to environmental change.

(11)
Pilocarpine induces salivary secretion and thirst in rats.
Kiyotoshi Inenaga (Kyushu Dental College)
(12)
Electrophysiological analysis of the afferent activity from the submandibular salivary gland in the rat.
Ryuuji Matsuo (Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical Sciences)
(13)
Effects of autonomic denervation and administration of SNI-2011 on the expression of AQPs in the rat salivary gland.
Xuefei Li (Institute of Health Biosciences, Tokushima University Graduate School)
(14)
Neural- and hormonal-induced protein synthesis and mitotic activity and the dependence on NO-generation.
Jörgen Ekstrüm (Göteborg University)
P16:
Relationship of chewing-stimulated whole saliva flow rate and salivary gland size in humans.
Kentaro Ono (Kyushu Dental College)
P17:
Cardiac-related activity in superior salivatory nucleus neurons in anaesthetized rats.
Ken’ichi Ishizuka (Nippon Dental University School of Life Dentistry at Niigata)
(15)
Electrophysiological study on the descending excitatory synaptic inputs to the superior salivatory nucleus in the rat.
Yoshihiro Mitoh (Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical Sciences)
(16)
Functions, regulation and mechanisms of action of SUMOylation in salivary cells.
David K Ann (Norris Cancer Center, University of Southern California)
P18:
Electrophysiological study of the inhibitory inputs from the forebrain and brainstem to the superior salivatory nucleus in rats.
Akihito Fujii (Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical Sciences)
P19:
Role of the feeding center for submandibular salivary secretion during feeding behavior in the rat.
Miyuki Kobashi (Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical Sciences)
P20:
The facial nerve and its influence on the parotid gland.
Nina Khosravani (Güteborg University)
P21:
Melatonin-evoked protein secretion from the rat parotid gland in vivo.
Hülay Çevik Aras (Güteborg Univeersity)
P22:
Induction of general anesthesia with propofol increases salivary flow.
Hajime Ishibashi (Nihon University School of Dentistry at Matsudo)
P23:
Salivary secretion by MR3-KO mice.
Minoru Matsui (Institute of Medical Sciences, University of Tokyo)

D. Structural differentiation and functional expression of salivary gland.

(17)
Regulation of epithelial tube formation in developing mouse submandibular gland.
Yohki Hieda (Osaka University Graduate School of Sciences)
(18)
FGF10 regulates branching morphogenesis during salivary gland development.
Matthew Hoffman (National Institute of Dental and Craniofacial Research, NIH, DHHS)
(19)
Involvement of a subtilisin-like proprotein convertase, PACE4, in branching morphogenesis and AQP5 expression in the rat embryonic submandibular gland.
Tetsuya Akamatsu (Institute of Health Biosciences, Tokushima University Graduate School)
P24:
Freeze fracture studies of tight junctions in mouse salivary glands and cultured salivary cell lines.
Kenichiro Kikuchi (Nippon Dental University School of Life Dentistry at Tokyo)
P25:
Shared or non-overlapping intracellular signaling pathways activated by EGFR or FGFR differentially regulate branching morphogenesis in fetal mouse submandibular glands.
Masanori Kashimata (Asahi University School of Dentistry)
P26:
Cellular aspect of salivary gland branching morphogenesis.
Yuichi Kadoya (Kitasato University School of Medicine)
P27:
The expression of cellular markers of duct/acini and side population dynamics in the duct-ligated mouse submandibular gland.
Nunuk Purwanti (Institute of Health Biosciences, Tokushima University Graduate School)
P28:
Role of PDGF in salivary gland morphogenesis.
Shinya Yamamoto, Satoshi Fukumoto (Kyushu University Faculty of Dental Science)
P29:
The change of the subcellular localization of CD38 in the rat sublingual gland during saliva secretion.
Wataru Masuda (Kyushu Dental College)
(20)
Submandibular and sublingual glands in Nkx2-3 mutant mice.
Arthur Hand (University of Connecticut Health Center)
(21)
A novel mouse protein differentially regulated by androgens in the submandibular and lacrimal glands.
Shoichi Iseki (Kanazawa University Graduate School of Medical Science)
(22)
Identification and therapeutic potential of salivary gland side population cells.
Kenjji Mishima (Tsurumi University School of Dental Medicine)
P30:
Heat shock protein 27kDa (Hsp27) regulates differentiation and regeneration of acinar cells of the rat submandibular gland.
Osamu Amano (Meikai University School of Dentistry)
P31:
Temporary accumulation of glycogen in the epithelial cells during developmental differentiation of the mouse submandibular gland revealed by the high-pressure freezing/freeze substitution-TEM.
Sachiko Matsuura (Matsumoto Dental University)
P32:
Effects of actin-related drugs on exocytosis in parotid acinar cells.
Miwako Matsuki (Nihon University School of Dentistry at Matsudo)
P33:
Control of paracellular transport and its morphological evidence in perfused rat submandibular gland.
Sadamitsu Hashimoto (Tokyo Dental College)
P34:
Localization of G proteins in the main excretory duct of the rat submandibular gland with special reference to the MED tuft cell and the taste bud type II cell.
Atsuko Sato (Fukuoka Dental College)

E. Functional morphology of secretory granules

(23)
Ultrastructure of the ovine parotid gland.
Bernard Tandler (Case Western Reserve University School of Medicine)
(24)
A morphometric study by HRSEM of the secretory responses of human salivary glands stimulated in vitro by various secretagogues.
Alessandro Riva (Cagliari Univ)
(25)
Expresssion and function of aquaporin-6 in the rat salivary glands.
Hiroshi Sugiya, Miwako Matsuki (Nihon University School of Dentistry at Matsudo)
(26)
Analysis of secretory dynamics in mouse parotid acinar cells reveals multiple pathways for secretory granule fusion.
David Giovannucci (University of Toledo Health Science Center)
P35:
Relation of proteoglycan to sorting amylase into secretory granules/vesicles.
Tomoko Nashida (Nippon Dental University School of Life Dentistry at Niigata)
P36:
Activation of cAMP-dependent protein kinase by cGMP in the rat parotid acinar cells.
Hiromi Shimomura (Nippon Dental University School of Life Dentistry at Niigata)
P37:
Roles of Rab27 and its effectors in isoproterenol-induced amylase release from rat parotid acinar cells.
Akane Imai (Nippon Dental University School of Life Dentistry at Niigata)
P38:
Subtype-specific regulation of inositol (1,4,5)- trisphosphate receptors by protein kinase A.
Matthew J Betzenhauser (Rochester University)
P39:
Exocytosis and fluid secretion in exocrine glands studied by two-photon microscopy.
Tomomi Nemoto (National Institute for Physiological Sciences, NINS)
P40:
Multi-photon imaging of cellular heterogeneity in the sensitivity of Ca2+ responses in rat parotid ducts.
Akiko Shitara (Health Sciences University of Hokkaido School of Dentistry)
P41:
Morphological changes induced by histatins in Candida albicans: A microscopic and submicroscopic comparison.
Raffaella Isola (Cagliari University)
P42:
Sequential appearance of Golgi proteins during de novo formation of the Golgi apparatus in parotid acinar cell.
Hideaki Tamaki (Kitasato University School of Medicine)
P43:
Comparison of cluster formation of GFP-IP3 receptors in HSY, a human salivary cell line, and COS-7 cells.
Yosuke Tojyo (Health Sciences University of Hokkaido School of Dentistry)
P44:
Possible Involvement of Myosin-ATPase in the spatio-temporal regulation of exocytosis in adrenal chromaffin cells.
Konosuke Kumakura (Life Science Institute, Sophia University)

F. Control for fluid/electrolyte transport via trans-/paracellular routes.

(27)
The ion and fluid secretion mechanism.
James Melvin (Rochester University)
(28)
Structural and functional significance of the dimerization of the secretory Na-K-2Cl cotransporter (NKCC1).
R James Turner (National Institute of Dental and Craniofacial Research, NIH)
(29)
Localization and function of CLCA in rat submandibular glands.
Jun Yamazaki (Fukuoka Dental College)
P45:
Bond graph expression on an epithelial transport system.
Yusuke Imai (Osaka Medical College)
P46:
A modular approach to computational modelling of epithelial electrolyte transport.
Martin C Steward (Manchester University Faculty of Life Sciences)
P47:
Bicarbonate secretion by cultured salivary gland cells.
Varga Gabor (Hungarian Academy of Sciences-Semmelweis University Joint Research Organization)
P48:
Regulation of Cl secretion by muscarinic cholinergic and adrenergic stimulation in acinar cells of rat salivary gland.
Chikara Hirono (Hiroshima University Graduate School of Biomedical Sciences)
P49:
Voltage-dependent transient activity of Na+/H+ exchanger.
Yoshiro Sohma (Osaka Medical College)
(30)
A feedback control model of fluid transport in salivary gland.
A E Hill (Physiological Laboratory Cambridge University)
(31)
Evidence for interaction between transcellular and paracellular water transport pathways: signaling between Aquaporin-5 and the tight junction complex in mouse salivary glands.
Anil G Menon (Cincinnati University)
(32)
Change of claudin expression in primary cultured parotid acinar cells.
Junko Yoshigaki (Nihon University School of Dentistry at Matsudo)
P50:
Impaired aquaporin-5 distribution in salivary glands from a Sjögren’s syndrome mouse model.
Christine Delporte (Free University of Brussels)
P51:
Molecular and cellular analyses of mutant AQP5 which occurreDNAturally in Sprague-Dawley rats.
Mileva R Karabasil (Institute of Health Biosciences, Tokushima University Graduate School)
P52:
Regulation of intercellular junctions in polarized salivary cells.
Retsu Mitsui (Nihon University School of Dentistry at Matsudo)
P53:
The use of gene disruptions and isolated, perfused glands to examine mouse submandibular function.
Tetsuji Nakamoto (Rochester University Medical Center)
P54:
Water permeability as measured by NMR in salivary gland cells.
Yoshiteru Seo (Dokkyo University School of Medicine)

G. Stimulus-Secretion Coupling for starting electrolyte transport

(33)
Calcium signaling mechanisms in salivary gland cells and other epithelial cells.
James W Putney Jr (National Institute of Environmental Health Sciences)
(34)
Monitoring IP3 and Ca2+ dynamics in salivary and other cell lines.
Akihiko Tanimura (Health Sciences University of Hokkaido School of Dentistry)
(35)
Intracellular calcium signaling: mechanistic insight from analysis of distinct signals in parotid and pancreas.
David I Yule (Rochester University School of Medicine and Dentistry)
(36)
Regulation of the plasma membrane Ca2+-ATPase in parotid acinar cells.
Jason Bruce (Manchester University Faculty of Life Sciences)
P55:
Muscarinic receptor mobilization of plasma membrane Ca2+-ATPase in epithelial cells: Role of the NHERF2 PDZ scaffold.
Philip Poronnik (Queensland University School of Biomedical Sciences and Pharmacy)
P56:
Regulation of KCNQ2/3 by the ubiquitin ligase Nedd4-2.
Jenny Ekberg (Queensland University School of Biomedical Sciences and Pharmacy)
P57:
Secretagogues stimulate phosphorylation of MARCKS in parotid acinar cell.
Keitaro Satoh (Nihon University School of Dentistry at Matsudo)
(37)
Regulation of TRPC channels by STIM1.
Shumuel Muallem (University of Texas Southwestern Medical Center)
(38)
Shank2 as a key regulator of epithelial transport in apical membrane.
Min Goo Lee (Yonsei University College of Medicine)
(39)
The regulation of the epithelial Na+ channels by UTP.
David I Cook (Sydney University School of Medical Sciences)
(40)
Signaling pathways regulating Na+ transport in salivary ducts.
Anuwat Dinudom (Sydney University School of Medical Sciences)
P58:
Ca2+ influx induced by ionomycin under a high [K+]o in rat submandibular acinar cells.
Hideyo Yoshida (Osaka Medical College)
P59:
Regulation of the epithelial sodium channel by caveolin.
Il-Ha Lee (Sydney University School of Medical Sciences)
P60:
The role of TRP channel in the salivary gland fluid secretion.
Xibao Liu (National Institute of Dental and Craniofacial Research, NIH)

【参加者名】
14ヶ国から50名,国内から70名の唾液腺分野の第一線研究者が集い講演40題,ポスター60題が発表された。参加者のうち発表者を演題とともに上に列挙した。その他参加した共同研究者および参加者を次に列挙する。山科正平(北里大学医学部),下野正基(東京歯科大学),細井和雄(徳島大学大学院),Ding Wei(南京医科大学),Francisco Loy (Cagliari University),Bruria Shachar-Hill (Cambridge University),中西康夫(大阪大学),池田理恵(日本歯科大学),小山典子(朝日大学),大野健司(朝日大学),加藤靖浩(東京歯科大学),林美樹夫(関西医科大学),金剛寛泰(広島大学大学院),桜井健(日本大学松戸歯学部),藤原 優(札幌IDL),伊藤禎二(札幌IDL),新間秀一(岡崎統合バイオサイエンスセンター),杉浦悠毅(岡崎統合バイオサイエンスセンター),大橋正人(岡崎統合バイオサイエンスセンター),富永真琴(岡崎統合バイオサイエンスセンター)

【概要】
 本研究会は,日本学術振興会平成18年国際学術集会助成事業として,第3回ニールス・ステンセン記念国際唾液腺シンポジウムおよび36回生理研コンファレンスと合同で10月20日から2/3日の会期で自然科学研究機構岡崎コンファレンスセンターにて開催された。

 本会は対象を唾液腺に限定し,形態学,生理学,生化学,薬理学,病理学,細胞生理学の研究者達の成果のすりあわせを同じテーブルで行い,新しい概念を模索し臨床応用へ連結する芽を育むことを目的とした。アブストラクト集は別途作成し会議中に配布した。また会議後拡大アブストラクトを作成しCD-ROMに収納,ホームページhttp://www.nips.ac.jp/~masataka/stensen/stensen.htmlから閲覧可能とした。本年報ではシンポジウム/研究会の各セッションのサマリーを以下に記載した。

 生理学研究所は2007年創立30周年を迎え,長く岡崎市民には大きな支援を受けてきた。本会ではその恩返しと基礎研究を市民に理解していただくため,市民公開講座と市民公開演奏会を開催し,歴史的な学問の基盤と国際的な広がりを体感していただいた。会場の岡崎コンファレンスホールにシンポジウム参加者と岡崎市民,岡崎3研究所の職員,高校生ら約200名が参加し,講演とリュートの演奏を味わった。

 

A. 唾液による化学診断と分泌蛋白のプロテオミクス

 唾液を臨床データとして取扱うための重要な合意として,唾液分泌速度と唾液中の基質濃度の関係図を作成し,この相関から評価すべきことが議論された。分泌蛋白/ペプチドの分析がこの5年間のマススペクトロスコピーの技術革新で本格的に稼働し始めた。分泌蛋白は細胞内分泌顆粒内で貯蔵され,細胞から分泌され,導管を通る間にも修飾をうけ,さらに口腔内でも修飾を受けることが議論され,数多くのフラグメントについても将来の研究課題として残された。

 

B. 唾液機能を付与するための遺伝子治療

 喉頭がん,咽頭がんなどの放射線治療により唾液腺の腺房など分泌終末の機能が失われる。腺房の機能を導管に肩代わりさせ,水分分泌機能を加えるプロジェクトが本年アメリカ公衆衛生院(NIH) で開始された。基礎研究が具体的な臨床応用に発展した希有の例であり,聴衆を大きく勇気づけた。

 

C. 環境変化に応じた唾液分泌調節の神経機構

 従来あまり問題にされていなかった唾液腺からの求心性信号の存在が確定され,これがどのように中枢に作用し,唾液分泌を統御するか次に探索することとなった。唾液減少症に用いられるピロカルピンが脳室周囲系を刺激し「口渇」を誘導することが示された。このため,体液量調節の観点から,本薬の唾液分泌作用との関連が複雑になることが指摘され,本薬を含む研究の問題点が明らかになった。

 

D. 唾液腺構造分化と機能発現

 唾液腺が発達段階で枝をはり,管腔を形成する。唾液腺での幹細胞を探索し,これを唾液腺機能不全患者に自己移植し機能を回復させてゆくことは唾液腺分野の組織工学者の目標である。本会では幹細胞の探索の成果,接着分子の細胞内骨格の制御が討議された。

 

E. 分泌顆粒の機能形態

 分泌顆粒が均一ではなく下部構造をもつことは既に報告されてきたが,今回,グリコーゲンの沈着が幼少期の唾液腺分泌顆粒の傍らに発見され,顆粒の成熟との関係が注目された。また顆粒のアクアポリン6は陰イオン輸送を介し分泌顆粒内物質の濃縮を制御することが議論された。

 

F. 経/傍細胞輸送調節

 細胞からの水分分泌と細胞の間を通過する傍細胞輸送による水分分泌について,アクアポリン5を浸透圧受容体としてその信号により傍細胞経路が開閉する説が初めて国際学会で発表され高く評価され,具体的な実験プランも直接研究者間で検討された。

 

G. 分泌開始を誘導する細胞内信号系

 Ca信号系について12年前に岡崎で開催された唾液腺ワークショップからの研究史が総括され,細胞内Caストアの実態として連結した小胞体のアイデアが提出,今後細胞内信号系の実態を微細形態学で観測する手法が話し合われた。

 


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