| Project/Area Number |
04454249
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Tohoku University |
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Principal Investigator |
SHIMURA Sanae Tohoku Univ.Hospital Lecuterer, 医学部・附属病院, 講師 (20154312)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Hidetada Tohoku Univ.Hospital Professor, 医学部・附属病院, 教授 (20154312)
OKAYAMA Hiroshi Tohoku Univ.Hospital Assistant, 医学部・附属病院, 助手 (10160730)
KAKUTA Yasunori Tohoku Univ.Hospital Assistant, 医学部・附属病院, 助手 (80142933)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1992: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | Airway submucosal glands / Patch clamp / K+ channels / Cl- channels / Current response / IP3 / Cl- secretion / cyclic ADP ribose / ヒト / 気管 / 気管支 / 粘膜下腺 / クロライドチヤンネル / 細胞内セカンドメッセンジヤ- / 気道 / クロライド分泌 / パッチクランプ法 / K^+-チャンネル / Cl^--チャンネル / Na^+ / K^+ポンプ / グルココルチコイド / IP_3受容体 / IP_3感受性Ca^<++>プール / カフェイン感受性Ca^<++>プール / [Ca^<++>]i / M_3ムスカリン受容体 |
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| Research Abstract |
We examined ion channels and current responses to agonists in acinar cells of human and feline airway submucosal glands using patch clamp analysis. Ca^<2+>-sensitive K^+- (164 pS) and Cl^--channels (4,15 pS) were observed in basolateral and apical membranes, respectively. M3-, P2- and NK1/2 -receptor stimulations induced a [Ca^<2+>]i-rise and resultant Cl^--secretion which was mimicked by the application of intracellular IP^3. Immunohistochemical analysis revealed the localization of IP^3 receptors on both the cytosol and some regions of the endoplasmic reticulum beneath the apical membrane of acinar cells. Caffeine and intracellular ryanodine induced a K^+ current alone without Cl^- current, which were mimicked by the application of intracellular cADPribose. This suggests that cADPribose regulates Ca^<2+>-induced Ca^<2+> release. Monoclonal antibodies to the IP^32-receptor abolished both induced K^+ and Cl^- currents. These results indicate that apically localized IP^3 receptors control Cl^- secretion from airway submucosal gland cells and that K^+ -current maintains the Cl^--secretion. Neither isoproterenol nor raising [cAMP]i induced any current. However, [cAMP]i-rise augmented P2-receptor stimulation induced Cl^--secretion.
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