Elucidation of mechanisms for the decrease in kallikrein secretion in isolated renal connecting tubular cells and examination of salt sensitivity on polymorphisms

• Project/Area Number: 20590983
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kitasato University
• Principal Investigator: FUJITA Tomoe Kitasato University, 医学部, 講師 (20296510)
• Co-Investigator(Kenkyū-buntansha): MAJIMA Masataka 北里大学, 医学部, 教授 (70181641)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: マイクロダイセクション / 腎接合尿細管 / 腎カリクレイン / カルシウムイメージング / SV40ラージT抗原遺伝子導入ラット / 遺伝子多型 / 自然発症高血圧ラット / SV40ラージT抗原ラット / 接合尿細管継代培養 / カリクレイン分泌 / 食塩感受性高血圧 / 賢接合尿細管 / カルシウム動態 / 不死化遺伝子導入ラット / 多型

Research Abstract

(1) We have established a calcium imaging model on primary cultured rat renal connecting tubules. Vasopressin increases intracellular calcium via a V1a receptor. (2) We have tried to obtain monoclonal cells of the kallikrein secreting cell by maximum diluting cultured cells derived from the renal initial collecting tubules isolated from SV40 large T antigen transgenic rats. Most of the cultured cells were intercalated cells and kallikrein secreting cells were few. (3) Six subjects among the 77 healthy Japanese volunteers have the polymorphism in the renal kallikrein promoter. Urine kallikrein activity was lower and sodium excretion was higher after water loading in the subjects with the promoter polymorphism than the subjects without the polymorphism.

Research Products

• [Journal Article] Microdose study of a P-glycoprotein substrate, fexofenadine, using a non-radioisotope-labelled drug and LC/MS/MS. (2010)
  • Author(s): Yamazaki A, Kumagai Y, Yamane N, Tozuka Z, Sugiyama Y, Fujita T, Yokota S, Maeda M
  • Journal Title: J Clin Pharm Ther 35 Pages: 169-175
  • Peer Reviewed
• [Journal Article] Estimating the Contribution of Genes to Variation in Renal Drug Clearance by Active Secretion Using Multiple Data From Clinical Phase I Studies. (2010)
  • Author(s): Fujita T, Kumagai Y, Nakahara I, Ohtani Y, Majima M
  • Journal Title: J Clin Pharmacol 50/1 Pages: 109-114
  • Peer Reviewed
• [Journal Article] Microdose study of a P-glycoprotein substrate, fexofenadine, using a non-radioisotope-labelled drug and LC/MS/MS (2010)
  • Author(s): Yamazaki A, Kumagai Y, Yamane N, Tozuka Z, Sugiyama Y, Fujita T, Yokota S, Maeda M.
  • Journal Title: J Clin Pharm Ther Volume: Feb-35 Pages: 169-175
  • Peer Reviewed
• [Journal Article] Estimating the Contribution of Genes to Variation in Renal Drug Clearance by Active Secretion Using Multiple Data From Clinical Phase I Studies. (2010)
  • Author(s): Fujita T, Kumagai Y, Nakahara I, Ohtani Y, Majima M.
  • Journal Title: J Clin Pharmacol 50/1 Pages: 109-114
  • Peer Reviewed
• [Journal Article] An ATP-sensitive potassium channel blocker suppresses sodium-induced hypertension through increased secretion of urinary kallikrein. (2009)
  • Author(s): Kamata Y, Fujita T, Kato T, Hayashi I, Kurosaka M, Katori M, Fujita Y, Majima M
  • Journal Title: Hypertens Res 32(3) Pages: 220-226
  • NAID: 10024830128
  • Peer Reviewed
• [Journal Article] Safety, tolerability and pharmacokinetics of TAS-108, a novel anti-oestrogen, in healthy post-menopausal Japanese women : a phase I single oral dose study. (2009)
  • Author(s): Kumagai Y, Fujita T, Ozaki M, Yokota S, Maeda M, Shida M, Otani Y, Yamaya H, Tsuruta H
  • Journal Title: Basic Clin Pharmacol Toxicol 104/5 Pages: 352-359
  • Peer Reviewed
• [Journal Article] Levofloxacin注射剤500mg単回投与の健康被験者におけるQT間隔に対する影響 (2009)
  • Author(s): 杉山篤,福田涼子,毛利光志,藤田朋恵,熊谷雄治
  • Journal Title: 日本化学療法学会雑誌 57/2 Pages: 106-114
  • NAID: 10024798659
  • Peer Reviewed
• [Journal Article] Safety, tolerability and pharmacokinetics of TAS-108, a novel anti-oestrogen, in healthy post-menopausal Japanese women : a phase I single oral dose study. (2009)
  • Author(s): Kumagai Y, Fujita T, Ozaki M, Yokota S, Maeda M, Shida M, Otani Y, Yamaya H, Tsuruta H.
  • Journal Title: Basic Clin Pharmacol Toxicol 104/5 Pages: 352-359
  • Peer Reviewed
• [Journal Article] An ATP-sensitive potassium channel blocker suppresses sodium-induced hypertension through increased secretion of urinary kallikrein. (2009)
  • Author(s): Kamata Y, Fujita T, Kato T, Hayashi I, Kurosaka M, Katori M, Fujita Y, Majima M.
  • Journal Title: Hypertens Res 32(3) Pages: 220-226
  • NAID: 10024830128
  • Peer Reviewed
• [Journal Article] Contribution of down regulation of intestinal and hepatic cytochrome P450 3A to increased absorption of cyclosporine A in a rat nephrosis model. (2008)
  • Author(s): Tomoe Fujita, Shuichi Yasuda, Yuji Kamata, Kazumi Fujita, Yoshio Ohtani, Yuji Kumagai, Masataka Majima
  • Journal Title: J Pharmacol Exp Ther 327(2) Pages: 592-599
  • Peer Reviewed
• [Journal Article] 有機アニオン性尿毒症毒素インドキシル硫酸腎排泄への腎尿細管分泌の大きな寄与-L-トリプトファン経口負荷投与後健常成人での検討- (2008)
  • Author(s): 藤田朋恵,石原和彦,藤田和己,池田康彦,大谷義夫,熊谷雄治,馬嶋正隆
  • Journal Title: 臨床薬理の進歩 No.29 Pages: 106-112
• [Journal Article] Are all individuals equally sensitive in the blood pressure to high salt intake? (Review article). (2008)
  • Author(s): Katori M, Majima M
  • Journal Title: Acta Physiol Hung. 95(3) Pages: 247-65
• [Journal Article] A role of the renal kallikrein-kinin system in the kidney. (2008)
  • Author(s): Katori M, Majima M
  • Journal Title: Acta Physiol Hung. 95(1)
• [Presentation] 日本人及び中国人(漢民族)を対象とした1施設による薬物動態比較試験の実施体制の検討-企画・立案から実施までの課題- (2010)
  • Author(s): 前田実花、野村今日子、脇坂真美、江旻、王国琴、小林真美、高橋賢成、藤田朋恵、池田康彦、黒山政一、熊谷雄治
  • Organizer: 第31回日本臨床薬理学会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2010-12-03
• [Presentation] 日本人及び中国人(漢民族)でのアセトアミノフェン薬物動態の比較 (2010)
  • Author(s): 脇坂真美、江旻、池田康彦、藤田朋恵、高橋賢成、中村智美、斉藤由美子、前田実花、王国琴、佐藤美穂子、蓮沼智子、熊谷雄治
  • Organizer: 第31回日本臨床薬理学会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2010-12-03
• [Presentation] 日本人及び中国人(漢民族)を対象とした1施設による薬物動態比較試験の実施体制の検討-企画・立案から実施までの課題- (2010)
  • Author(s): 前田実花、野村今日子、脇坂真美、江旻、王国琴、小林真美、高橋賢成、藤田朋恵、池田康彦、黒山政一、熊谷雄治
  • Organizer: 第31回日本臨床薬理学会
  • Place of Presentation: 京都国際会議場(京都府)
  • Year and Date: 2010-12-03
• [Presentation] 日本人及び中国人(漢民族)でのアセトアミノフェン薬物動態の比較 (2010)
  • Author(s): 脇坂真美、江旻、池田康彦、藤田朋恵、高橋賢成、中村智美、斉藤由美子、前田実花、王国琴、佐藤美穂子、蓮沼智子、熊谷雄治
  • Organizer: 第31回日本臨床薬理学会
  • Place of Presentation: 京都国際会議場(京都府)
  • Year and Date: 2010-12-03
• [Presentation] 尿細管分泌の面からみた有機アニオン性尿毒症惹起物質インドキシル硫酸とアンジオテンシン変換酵素阻害薬との生体内での相互作用 (2010)
  • Author(s): 藤田朋恵、石原和彦、安田修一、熊谷雄治、馬嶋正隆
  • Organizer: 第31回日本臨床薬理学会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2010-12-02
• [Presentation] 腎尿細管分泌の面からみた有機アニオン性尿毒症惹起物質インドキシル硫酸とアンジオテンシン変換酵素阻害薬との生体内での相互作用 (2010)
  • Author(s): 藤田朋恵、石原和彦、安田修一、熊谷雄治、馬嶋正隆
  • Organizer: 第31回日本臨床薬理学会
  • Place of Presentation: 京都国際会議場(京都府)
  • Year and Date: 2010-12-02
• [Presentation] 臨床薬理試験参加希望者の検査データの年次調査1-血算- (2010)
  • Author(s): 中村智美、石崎沙織、高橋賢成、前田実花、黒山政一、田ケ谷浩邦、池田康彦、藤田朋恵、熊谷雄治
  • Organizer: 第31回日本臨床薬理学会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2010-12-01
• [Presentation] 臨床薬理試験参加希望者の検査データの年次調査1-血算- (2010)
  • Author(s): 中村智美、石崎沙織、高橋賢成、前田実花、黒山政一、田ケ谷浩邦、池田康彦、藤田朋恵、熊谷雄治
  • Organizer: 第31回日本臨床薬理学会
  • Place of Presentation: 京都国際会議場(京都府)
  • Year and Date: 2010-12-01
• [Presentation] Phase 1 Study of the Safety, Pharmacokinetics and Pharmacodynamics of Teneligliptin, a New DPP-IV Inhibitor, in Healthy Volunteers. (2010)
  • Author(s): 熊谷雄治, 藤田朋恵, 川口敦弘, ら
  • Organizer: American Diabetes Association's 70th Scientific Sessions
  • Place of Presentation: Orlando, FL(米国)
  • Year and Date: 2010-06-28
• [Presentation] Phase 1 Study of the Safety, Pharmacokinetics and Pharmacodynamics of Teneligliptin, a New DPP IV Inhibitor, in Healthy Volunteers (2010)
  • Author(s): Yuji Kumagai, Tomoe Fujita, Atsuhiro Kawaguchi, ら
  • Organizer: American Diabetes Association's 70th Scientific Sessions
  • Place of Presentation: Orlando, FL(米国)
  • Year and Date: 2010-06-28
• [Presentation] 新規DPP-IV阻害薬teneligliptinの健康成人における薬物動態及び薬理学的効果 (2010)
  • Author(s): 川口敦弘,林義治,近藤和興,藤田朋恵,熊谷雄治
  • Organizer: 第53回日本糖尿病学会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2010-05-27
• [Presentation] 新規DPP-IV阻害薬teneligliptinの健康成人における薬物動態及び薬理学的効果 (2010)
  • Author(s): 川口敦弘, 林義治, 近藤和興, 藤田朋恵, 熊谷雄治
  • Organizer: 第53回日本糖尿病学会
  • Place of Presentation: 岡山コンベンションセンター(岡山県)
  • Year and Date: 2010-05-27
• [Presentation] The relationship among PK/PD profiles of Aliskiren administered orally after meal in Japanese patients with essential hypertension (2009)
  • Author(s): Yuji Kumagai, Shigeto Kanada, Tomoe Fujita, Masayuki Yamaguchi, Sayaka Shimada, Kaneo Sekiguchi
  • Organizer: 第30回日本臨床薬理学会年会
  • Place of Presentation: パシフィコ横浜会議センター
  • Year and Date: 2009-12-04
• [Presentation] The relationship among PK/PD profiles of Aliskiren administered orally after meal in Japanese patients with essntial hypertension (2009)
  • Author(s): Yuji Kumagai, Shigeto Kanada, Tomoe Fujita, Masayuki Yamaguchi, Sayaka Shimada, Kaneo Sekiguchi
  • Organizer: 日本臨床薬理学会年会
  • Place of Presentation: パシフィコ横浜会議センター(横浜)
  • Year and Date: 2009-12-04
• [Presentation] Elevation of intracellular calcium in response to vasopressin and bradykinin in primary cultured rat isolated renal connecting tubule segments. (2009)
  • Author(s): Yuji Kamata, Tomoe Fujita, Shuichi Yasuda, Yoshikuni Fujita, Masataka Majima
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-03-18
• [Presentation] Elevation of intracellular calcium in response to vasopressin and bradykinin in primary cultured rat isolated renal connecting tubule segments (2009)
  • Author(s): Yuji Kamata, Tomoe Fujita, Shuichi Yasuda, Yoshikuni Fujita, Masataka Majima
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-03-18
• [Presentation] 臨床研究/臨床試験コーディネーター(CRC)教育・研修プログラムに関する検討(1)-CRC教育・研修ラダーシートの検討と構築- (2008)
  • Author(s): 前田実花、横田愼一、野村今日子、藤田朋恵、池田康彦、高橋賢成、小川幸雄、黒山政一、佐藤敏彦、熊谷雄治
  • Organizer: 第29回日本臨床薬理学会年会
  • Place of Presentation: 東京
  • Year and Date: 2008-12-06
• [Presentation] 医薬品承認用量の国際比較 第I報-日本と中国の比較- (2008)
  • Author(s): 江旻、熊谷雄治、藤田朋恵、馬嶋正隆
  • Organizer: 第29回日本臨床薬理学会
  • Place of Presentation: 東京
  • Year and Date: 2008-12-04