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Development of the modulator drug specifically targeting biomechanical reaction in the circulatory system and the application for experimental therapeutics.

Research Project

Project/Area Number 08557139
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 医薬分子機能学
Research InstitutionUniversity of Shizuoka

Principal Investigator

NAKAYAMA Koichi  Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Shizuoka, Professor, 薬学部, 教授 (50112769)

Co-Investigator(Kenkyū-buntansha) TANABE Yoshiyuki  Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Sh, 薬学部, 助手 (10275109)
OBARA Kazuo  Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Sh, 薬学部, 講師 (60117611)
ASANO Toshio  Laboratory for Pharmaceutical Research, Institute for Life Science Research, Asa, 開発薬理研究所, 主任研究員
ISHII Kunio  Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Sh, 薬学部, 教授 (90137993)
TAKEISHI Keiichi  School of Food and Nutritional Sciences, University of Shizuoka, Professor, 食品栄養科学部, 教授 (90012608)
浅井 敏雄  旭化成工業(株), 開発薬理研究所, 主任研究員
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1997: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1996: ¥5,100,000 (Direct Cost: ¥5,100,000)
Keywordsmechano-transduction / biomechanics / tyrosine kinase inhibitor / protein tyosyl phosphorylation / cardiovascular system / myogenic contraction / hemodynamics / stretch / pressure / チロシンキナーゼ阻害薬 / 物理受容・応答 / 細胞内情報伝達 / 接着班キナーゼ活性 / 血管収縮
Research Abstract

Purpose The cardiovascular response to hemodynamic/biomechanical stimuli, including pressure and flow, is a type of physical reception and a subsequent intra/inter cellular signaling in the heart and blood vessels. Pathophysiological conditions, such as vasospasm, hypertension, and myocardial hypertrophy, are also caused by the abnormal biomechanical stimuli. In order to elucidate the mechanism for mechano-transduction and to develop a new modulator of biomechanical reaction in the cardiovascular system, the following experiments were undertaken : 1) intra/intercellular signaling mechanism of arterial tissues and cells isolated from brain artery and lung in response to pressure and stretch with the special regard to protein tyrosyl phosphorylation, intracellular Ca2+ concentration, and mechanical activity. 2) Search for a new modulator of the response to hemodynamic stimuli. 3) Experimental therapeutics in the monocrotaline-induced pulmonary hypertensive rats. Results and discussions A … More s to the mechanism for mechano-transduction, the following process could be suggested : The membrane depolarization and activation of L-type Ca2+ channels through protein tyrosyl phosphorylation of the mechano-gated channel triggers the mechanical activity. Morcover, platelet-derived growth factor receptor- b chain, a receptor type of tyrosine kinase, and an intracellular messenger, such as Rho, a low molecular GTP-binding protein, are specifically involved in the signaling of mechano-transduction. Future prospect The cardiovascular response to hemodynamic stimuli touch the core of up to-date problems, including regulation of blood pressure and flow, myogenic tone, mechano-gated ion channels, shear stress and endothelial function, and pathophysiological implications of high and low shear stress and hemodynamic overload. Our present studies will surely open the way to an era for the development of new cardiovascular drugs with a novel mechanism of action, and our general principle will improve the knowledge about the cardiovascular system in health and disease. Less

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (135 results)

All Other

All Publications (135 results)

  • [Publications] 生垣 一郎、佐藤 多恵、佐多 美奈子、浅野 敏雄: "蛋白リン酸化酵素阻害薬ファスジル(AT877)の血液凝固時間および血漿板に対する作用。" 薬理と治療 (Jpn.Pharmacol.Ther.),. 24,. 799-801 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 竹石 桂一: "白血病細胞の分化誘導時における細胞増殖必須遺伝子の発現抑制機構の解析。" 薬学の進歩 研究成果報告集. 12,. 107-115 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Koichi Nakayama, Kiichiro Ueta, Yoshio Tanaka, Yoshiyuki Tanabe and Kunio Ishii: "Stretch-induced contraction of rabbit isolated pulmonary artery and the involvement of endothelium-derived thromboxane A_2." Br.J.Phamacol.122. 199-208 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Naohiro Masumoto, Koichi Nakayama, Akihiro Oyabe, Mayumi Uchino, Kunio Ishii, Kazuo Obara and Yoshiyuki Tanabe: "Specific attenuation of the pressure-induced contraction of rat cerebral artery by herbimycin A." Eur.J.Pharmacol.330. 55-63 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsutomu Nakahara, Kunio Ishii, Yoshio Tanaka and Koichi Nakayama: "Flow-dependent regulation of nitric oxide formation in the isolated canine mesenteric arterial bed." Jpn.J.Pharmacol.74. 275-280 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Jane M.Lalli, Kazuo Obara and Richard J.Paul: "Vanadate oxidation activates contraction in skinned smooth muscle without myosin light chain phosphorylation." Am.J.Physiol.41. C278-C288 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsutomu Nakahara, Kunio Ishii, Yoshio Tanaka and Koichi Nakayama: "Flow regulates vasodilator responses to acetylcholine in the isolated canine mesenteric arterial bed." Biol.Pharm.Bull.20. 568-570 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kazuo Obara, Peggy S.Bowman, Yukisato Ishida and Richard J.Paul: "Effects of hypoxia on [Ca^<2+>]_i, pH_i and myosin light chain phosphorylation in guinea-pig taenia cacci." J.Physiol.503. 427-433 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshiyuki Tanabe, Chie Kohchi, Namiko Kitahara-Tanabe, Den'ichi Mizuno, Gen Ichiro Soma: "Involvement of 26-kDa membrane-bound tumour necrosis factor precursor in bidirectional feedback regulation on 17-kDa tumour necrosis factor production after stimulation by lipopolysaccharide." Cytokine. 10. 82-92 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Koichi Nakayama, Tohru Nakazawa, Yoshihisa Fukuta and Yoshio Tanaka: "Stereo-selective calcium antagonistic and binding propertics of the enantiomers of lemildipine in vascular tissue of pigs and dogs." Arzneim.-Forsch./Drug Res.46. 1045-1053 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsutomu Nakahara, Kunio Ishii, Yoshio Tanaka and Koichi Nakayama: "Infusion of pressor agents selectively attenuate depressor response to Ach in anethetized dogs." Am.J.Physiol.271. H273-H281 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kazuo Obara, Pawel T.Szymanski, Terence Tao and Richard J.Paul: "Effect of calponin on isometric force and shortening velocity in permeabilized tacnia coli smooth muscle." Am.J.Physiol.270. C481-C487 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsutomu Nakahara, Kunio Ishii, Yoshio Tanaka and Koichi Nakayama: "Involement of neurohumoral factors in the pressor mecchanism of NG-nitro-L-arginine." Eur.J.Pharmacol.287. 49-56 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshio Tanaka, Tohru Nakazawa, Hiromi Ishiro, Michihiro Saito, Hisayuki Uneyama, Scinosuke Iwata, Kunio Ishii and Koichi Nakayama: "Ca^<2+> handing mechanisms underlying neuropeptide Y-induced contraction in canine basilar artery." Eur.J.Pharmacol.289. 59-66 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kazuo Obara, Gordana Nikccvic, Lidija Pcstic, Grzegorz Nowak, Donald D.Lorimer, Vince Guerricro, Jr., Elliot L.Elson, Richard J.Paul and Primal de Lancrolle: "Fibroblast contractility without an increase in basal myosin light chain phosphorylation in wild type cells and cells expressing the catalytic domain of myosin light chain kinase." J.Biol.Chem.270. 18734-18737 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsutomu Nakahara, Kunio Ishii, Kenichiro Iwamoto and Koichi Nakayama: "Differential significance of nitric oxide in hypotensive mechanisms of acetylcholine and histamine in dogs." Res.Commun.Mol.Path.Pharmacol.89. 77-84 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hong Sheng, Kunio Ishii, Ulrich Fostermann and Ferid Murad: "Mechanism of bradykinin-induced cyclic GMP accumulation in bovine tracheal smooth muscle." Lung.73. 373-383 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshio Tanaka, Hiromi Ishiro, Tohru Nakazawa, Michihiro Saito, Kunio Ishii and Koichi Nakayama: "Potentiation by endothelin-1 of Ca^<2+> sensitivity of contractile elements depends on Ca^<2+> influx through L-type Ca^<2+> channels in the canine cerebral artery" Gen.Pharmac.26. 855-864 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hisayuki Uneyama, Yoshio Tanaka, Seinosuke Iwata, Tsuneo Ishiguro and Koichi Nakayama: "Pharmacological characteristics of the canine ccrrcbrovascular cinstriction produced by neuropeptide Y." Biol.Pharm.Bull.18. 501-506 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Satoh, Y.Yamamoto, Y.Toshima, Ikegaki, T.Asano, Y.Suzuki and M.Shibuya: "Fasudil, a protein kinase inhibitor, prevents the development of endothelial injury and neutrophil infiltration in a two- haemorrhage canine model." J.Clin.Neurosci.in press. (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshinori Toshima, Shin-ichi satoh, Ichiro Ikegaki, Toshio Asano, Yoshio Suzuki and Masato Shibuya: "Thromboxane A2 synthetase inhibitor failed to ameliorate the arterial narrowing during the chronic phase of ccrebral vasospasm." Life Sci.61(14). 1371-1377 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Naoki Katsumata, Hiroaki Shimokawa, Minoru Seto, Toshiyuki Kozai, Tohru Yamawaki, Kouichi Kuwata, Kensuke Egashira, Ichiro Ikegaki, Toshio Asano, Yasuharu Sasaki, Akira Takeshita: "Enhanced myosin light chain phosphorylations as a central mechanism for coronary artery spasm in a swine model with interleukin-Ib." Circulation. 96. 4357-4363 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Satoh, I.Ikegaki, Y.Suzuki, T.Asano, M.Shibuya and H.Hidaka: "Neuroprotective properties of a proreinkinase inhibitor against ischemia-induced neuronal damage in ratts and gerbils." Brit.J.Pharmacol.118. 1592-1596 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Maki Wakabayashi, Hideyuki Katai, Nobuyuki Horie and Keiichi Takeishi: "Cloning of the monkey thymidylate synthase gene and characterization of regulatory sequences in the promoter region." Nucleic Acids Symposium Series. 35. 227-228 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nobuyuki Horie and Keiichi Takeishi: "Identification of functional elements in the promoter region of the human gene for thymidylate synthase and nuclear factors that regulate the expression of the gene." J.Biol.Chem.272. 18357-18381 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Koichi Nakayama: "Stretch-induced contraction of rabbit isolated pulmonary artery and the involvement of endothelium-derived thromboxane A2." Br.J.Pharmacol.122. 199-208 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Naohiro Masumoto: "Specific attenuation of the pressure-induced contraction of rat cerebral artery by herbimycin A." Eur.J.Pharmacol.330. 55-63 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsutomu Nakahara: "Flow-dependent regulation of nitric oxide formation in the isolated canine mesenteric arterial bed." Jpn J.Pharmacol.74. 275-280 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Jane M.Lalli: "Vanadate oxidation activates contraction in skinned smooth muscle without myosin light chain phosphorylation." Am.J.Physiol.41. C278-C288 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsutomu Nakahara: "Flow regulates vasodilator responses to acetylcholine in the isolated canine mesenteric arterial bed." Biol.Pharm.Bull. 20. 568-570 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kazuo Obara: "Effects of hypoxia on [Ca^<2+>]i,pHi and myosin light chain phosphorylation in guinea-pig taenia caeci." J.Physiol.503. 427-433 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshiyuki Tanabe: "Involvement of 26-kDa membrane-bound tumor necrosis factor precursor in bidirectional feedback regulation on 17-kDa tumour necrosis factor production after stimulation by lipopolysaccharide." Cytokine. 10. 82-92 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Koichi Nakayama: "Pharmacological profile and therapeutic perspectives of semotiadil fumarate (SD-3211),a novel benzothiazine Ca^<2+> antagonist." Cardiovascular Drug Reviws. 14. 97-134 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Koichi Nakayama: "Stereo-selective calcium antagonistic and binding properties of the enantiomers of lemildipine in vascular tissue of pigs and dogs." Arzneim.Forsch/Drug Res.46. 1045-1053 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsutomu Nakahara: "Infusion of pressor agents selectively attenuate depressor response to ACh in anesthetized dogs." Am.J.Physiol.271. H273-H281 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kazuo Obara: "Effect of calponin on isometric force and shortening velocity in permeabilized taenia coli smooth muscle." Am.J.Physiol.270. C481-C487 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsutomu Nakahara: "Involvement of neurohumoral factors in the pressor mechanism of N^G-nitro-L-arginine." Eur.J.Pharmacol.287. 49-56 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshio Tanaka: "Ca^<2+> handling mechanisms underlying neuropeptide Y-induced contraction in canine basilar artery." Eur.J.Pharmacol.289. 59-66 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] 中山貢一: "抗高血圧薬Ca拮抗剤-開発の歴史." 生体の科学. 46. 678-683 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kazuo Obara: "Fibroblast contractility without an increase in basal myosin light chain phosphorylation in wild type cells and cells expressing the catalytic domain of myosin light chain kinase." J.Biol.Chem.270. 18734-18737 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsutomu Nakahara: "Differential significance of nitric oxide in hypotensive mechanisms of acetylcholine and histamine in dogs." Res.Commun.Mol.Path.Pharmacol.89. 77-84 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hong Sheng: "Mechanism of bradykinin-induced cyclic GMP accumulation in bovine tracheal smooth muscle." Lung. 73. 373-383 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshio Tanaka: "Potentiation by endothelin-1 of Ca^<2+> sensitivity of contractile elements depends on Ca^<2+> influx through L-type Ca^<2+> channels in the canine cerebral artery." Gen.Pharmac.26. 855-864 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hisayuki Uneyama: "Pharmacological characteristics of the canine cerebrovascular constriction produced by neuropeptide Y." Biol.Pharm.Bull.18. 501-506 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Satoh: "Fasudil,a protein kinase inhibitor,prevents the development of endothelial injury and neutrophil infiltration in a two-haemorrhage canine model." J.Clin.Neurosci.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshinori Toshima: "Thromboxane A2 synthetase inhibitor failed to ameliorate the arterial narrowing during the chronic phase of cerebral vasospasm." Life Sci.61.14. 1371-1377 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Naoki Katsumata: "Enhanced myosin light chain phosphorylations as a central mechanism for coronary artery spasm in a swine model with interleukin-1β." Circulation. 96. 4357-4363 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Satoh: "Neuroprotective properties of a protein kinase inhibitor against ischemia-induced neuronal damage in rats and gerbils." Br.J.Pharmacol.118. 1592-1596 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 生垣一郎: "蛋白リン酸化酵素阻害薬ファスジル(AT877)の血液凝固時間および血漿板に対する作用." 薬理と治療. 24. 799-801 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Maki Wakabayashi: "Cloning of the monkey thymidylate synthase gene and characterization of regulatory sequences in the promoter region." Nucleic Acids Symposium Series. 35. 227-228 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nobuyuki Horie: "Identification of functional elements in the promoter region of the human gene for thymidylate synthase and nuclear factors that regulate the expression of the gene." J.Biol.Chem.272. 18357-18381 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 竹石桂一: "白血病細胞の分化誘導時における細胞増殖必須遺伝子の発現抑制機構の解析." 薬学の進歩. 12. 107-115 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kazuo Obara: "Different Ca^<2+> dependent mechanisms of quick and slow stretch-induced contractions in vascular smooth muscle." J.Muscle Res.and Cell Motility. 17. 292-293 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kazuo Obara: "Uncoupling of force and myosin light chain phosphorylation produced by slow stretch involves Rho activity in canine basilar artery." Biophys.J.74・2. A258 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mayumi Uchino: "Identification of protein kinase C isoforms in porcine coronary artery and their involvement in contractile potentiation induced by endothelin-1." Jpn.J.Pharmacol.76・Suppl.I. 217 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 百瀬和享: "メカニカルストレスと細胞反応機構;その薬理学的立場でのアプローチ." 日薬理誌. 110. 123-125 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 笹瀬智彦: "イヌ脳底動脈単離平滑筋細胞における電位依存性カルシウムチャネルに対する浸透圧性伸展刺激の影響." 日薬理誌. 110. 77 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Koichi Nakayama: "Involvement of endothelium derived thromboxane A2 in the contractile response of isolated rabbit pulmonary artery to slow stretch." J.Muscle Res.and Cell Motility. 18. 497 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 増本直広: "ラット摘出大脳動脈における圧誘発性収縮に対するチロシンキナーゼ阻害薬の抑制作用." 血管. 20. 8 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kazuo Obara: "Involvement of myosin light chain kinase and tyrosine kinase activities in mechanotransduction by vascular smooth muscles." Jpn.J.Pharmacol.73・Suppl.I. 24 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hiroaki Nejishima: "Inhibitory mechanism of N^G-nitro L-arginine on acetylcholine-induced depressor responses in anesthetized dogs:Significance of elevated blood pressure." Jpn.J.Pharmacol.73・Suppl.I. 131 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Naohiro Masumoto: "Involvement of tyrosine kinase in pressure-induced contraction of rat cerebral artery." Jpn.J.Pharmacol.73・Suppl.I. 75 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mayumi Uchino: "Slow stretch stimulation uncouples myosin light chain phosphorylation and tension in canine basilar artery." Jpn.J.Pharmacol.73・Suppl.I. 203 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Koichi Nakayama: "Protein tyrosine kinase as a possible mechano-sensor in the genesis of the pressure-induced vascular contraction." J.Vasc.Res.34・S1. 30 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Koichi Nakayama: "Contributions of the sympathetic nervous and renin-angiotensin systems to the pressor mechanism of N^G-nitro-L-arginine in dogs." Jpn.J.Pharmacol.73・Suppl.I. 30 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kunio Ishii: "Regulation of the intracellular free calcium concentration of rat pancreatic β-cells via the NO-cGMP system." Jpn.J.Pharmacol.73・Suppl.I. 64 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 秋丸真司: "ラットにおける皮膚循環の薬理学的特性とprostaglandin E 製剤の作用について." 日薬理誌. 107. 10 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 湯山弘法: "単離ラット膵ランゲルハンス氏島β細胞内遊離Ca^<2+>濃度に対するNO-cGMP系活性化の影響." 日薬理誌. 107. 19 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 小原一男: "イヌ脳底動脈の緩徐伸展誘発性収縮におけるCa^<2+>起源について." 日薬理誌. 107. 73 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 植田 喜一郎: "家兎摘出肺動脈の伸展誘発性収縮における内皮由来プロスタノイドの関与" 日薬理誌. 107. 74 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 内野万有美: "イヌ脳底動脈における緩徐伸展刺激による張力発生に対するカリウムチャネル遮断薬の作用." 日薬理誌. 107. 118 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 山中章弘: "イヌ脳底動脈における伸展誘発性収縮とミオシン軽鎖のリン酸化." 血管. 19. 22 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 小原一男: "イヌ脳底動脈におけるカリウムチャネル遮断薬の緩徐伸展刺激応答促進作用." J.Smooth Muscle Res.32. 60 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 河内千恵: "TNF3'UTRポリAシグナル部分によるTNFの発現制御について." 生化学. 68. 954 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kazuo Obara: "Effects of calponin on isometric force and unloaded shortening velocity in skinned taenia coli smooth muscle." Jpn.J.Physiol.45・Suppl.S206-S207 (1995)

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      1997 Annual Research Report
  • [Publications] 植田喜一郎: "ウサギ摘出肺動脈の伸展誘発性収縮における内皮依存性について." 血管. 18. 14 (1995)

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      1997 Annual Research Report
  • [Publications] K.Obara: "Calponin inhibits shortening velocity and isometric force in skinned Taenia coli smooth muscle." Biophys.J.68. A75 (1995)

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      1997 Annual Research Report
  • [Publications] R.J.Paul: "Fibroblast contractility is not regulated by phosphorylation of myosin light chains." Biophys.J.68. A281 (1995)

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      1997 Annual Research Report
  • [Publications] 中山貢一: "薬理学研究新時代におけるin vivo/血液潅流標本実験の役割." Jpn.J.Pharmacol.67・Suppl.I. 35 (1995)

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  • [Publications] 椎 大介: "ウサギ骨格筋膜標本における|^3H|semotiadil fumarateの結合特性." Jpn.J.Pharmacol.67・Suppl.I. 96 (1995)

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  • [Publications] 中原 努: "麻酔イヌにおける昇圧物質持続注入後のアセチルコリンの降圧効果減弱におけるコリンエステラーゼの役割." Jpn.J.Pharmacol.67・Suppl.I. 268 (1995)

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  • [Publications] 小原一男: "イヌ脳底動脈における緩徐伸展刺激誘発性収縮とミオシン軽鎖のリン酸化の乖離について." 第74回日本生理学会大会予稿集. 341 (1997)

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      1997 Annual Research Report
  • [Publications] 松浦典子: "ラット膵ランゲルハンス氏島β細胞機能に対するNO-cGMP系の影響." 日本薬学会第117年会講演要旨集. 3. 41 (1997)

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      1997 Annual Research Report
  • [Publications] 笹瀬智彦: "イヌ脳底動脈単離平滑筋細胞における電位依存性カルシウムチャネルに対する浸透圧性伸展刺激の影響." 第96回日本薬理学会関東部会口演要旨集. 75 (1997)

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      1997 Annual Research Report
  • [Publications] 小原一男: "共焦点レーザー顕微鏡を用いた薬物の細胞内動態について." 第4回バイオ・メディカル光科学研究会講演要旨集. 11-12 (1997)

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      1997 Annual Research Report
  • [Publications] Koichi Nakayama: "Differential effects of stretching on the contractile signal transduction in vascular tissues." XXXIII International Congress of Physiological Sciences.Abstract. P079.01 (1997)

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      1997 Annual Research Report
  • [Publications] 増本直広: "ラット摘出大脳動脈における圧誘発性収縮に対するハービマイシンAの選択的抑制" 第43回日本薬学会東海支部総会講演要旨集. 16 (1997)

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      1997 Annual Research Report
  • [Publications] Kazuo Obara: "Contractile potentiation by endothelin-1 and protein kinase C isoforms." Fifth International Conference on Endothelin,Abstract. 42 (1997)

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      1997 Annual Research Report
  • [Publications] 木村 誠: "イヌ脳底動脈単離平滑筋細胞における浸透圧性伸展刺激による電位依存性カルシウム電流の増強." 第44回中部日本生理学会予稿集. 29 (1997)

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      1997 Annual Research Report
  • [Publications] 中山貢一: "肺動脈の力学刺激による内皮依存性収縮反応について." 第7回循環薬理研究会講演要旨集. 20 (1997)

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      1997 Annual Research Report
  • [Publications] Yoshiyuki Iwatsuki: "Pathology and function of heart and pulmonary artery in monocrotaline-induced pulmonary hypertension." The Third Japan-China International Symposium on Health Science,Program and Abstracts.20-21 (1997)

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      1997 Annual Research Report
  • [Publications] 藤田正一: "マクロファージ活性化における膜結合型TNFの役割とその作用機序の解明." 第20回日本分子生物学会年会講演要旨集. 2-157-P-305 (1997)

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      1997 Annual Research Report
  • [Publications] 木村 誠: "イヌ脳底動脈単離平滑筋細胞における電位依存性カルシウムチャネルに対する浸透圧変化の影響" 日本薬学会第118年会 講演要旨集. 9-84 (1997)

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      1997 Annual Research Report
  • [Publications] Yoshiyuki Tanabe: "Stretch-induced tyrosine phosphorylation in rabbit arteries and cultured vascular smooth muscle cells." XIIIth International Congress of Pharmacology,Abstract. 2 (1997)

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      1997 Annual Research Report
  • [Publications] Naohiro Masumoto: "The mechanosensory mechanism dependent on tyrosine kinase in pressure-induced myogenic contraction of rat cerebral artery." XIIIth International Congress of Pharmacology,Abstract. 3 (1997)

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      1997 Annual Research Report
  • [Publications] 中原 努: "麻酔イヌで観察される昇圧物質持続投与後の肺におけるアセチルコリン分解亢進." 第69回日本薬理学会年会 予稿集. 139 (1996)

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      1997 Annual Research Report
  • [Publications] 茅野大介: "Prostaglandin E1製剤の末梢循環改善作用:ラット後肢足底部皮膚における検討." 日本薬学会第116年会 講演要旨集. 3. 27 (1996)

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      1997 Annual Research Report
  • [Publications] 小原一男: "イヌ脳底動脈の緩徐伸展誘発性収縮におけるCa^<2+>起源について." 第94回日本薬理学会関東部会 口演要旨集. 49 (1996)

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      1997 Annual Research Report
  • [Publications] 植田喜一郎: "家兎摘出肺動脈の伸展誘発性収縮における内皮由来プロスタノイドの関与." 第94回日本薬理学会関東部会 口演要旨集. 52 (1996)

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      1997 Annual Research Report
  • [Publications] 松浦典子: "ラット膵ランゲルハンス氏島β細胞機能に対する環状ヌクレオチドの影響." 第3回バイオ・メディカル光科学研究会 講演要旨集. 19-20 (1996)

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      1997 Annual Research Report
  • [Publications] 茅野大介: "ラット後肢足底部の皮膚循環に対するPGE1製剤の作用." 第8回静岡県薬剤研究会 講演要旨集. 2 (1996)

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      1997 Annual Research Report
  • [Publications] 内野万有美: "イヌ脳底動脈における緩徐伸展刺激による張力発生に対するカリウムチャネル遮断薬の作用." 第94回日本薬理学会関東部会 口演要旨集. 60 (1996)

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      1997 Annual Research Report
  • [Publications] 石田行知: "好気的代謝阻害の平滑筋弛緩機構." 第119回日本獣医学会 講演要旨集. 57 (1995)

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      1997 Annual Research Report
  • [Publications] K.Obara: "Effects of calponin on isometric force and unloaded shortening velocity in skinned taenia coli smooth muscle." The Second Joint Meeting of the Physiological Societies of Japan and U.K.and Eire,Abstract. 187 (1995)

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      1997 Annual Research Report
  • [Publications] 林 賢一: "摘出モノクロタリン肺高血圧ラット肺動脈において観察された律動収縮について." 第92回日本薬理学会関東部会 要旨集. 75 (1995)

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      1997 Annual Research Report
  • [Publications] 小原一男: "イヌ脳底動脈における伸展誘発性収縮について." 第92回日本薬理学会関東部会 要旨集. 76 (1995)

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  • [Publications] 湯山弘法: "単離ラット膵ランゲルハンス氏島β細胞内遊離Ca^<2+>濃度変化のArgus 50システムによる解析:NO-cGMP系の関与について." 第2回バイオメディカル光科学研究会 講演要旨集. 18-19 (1995)

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      1997 Annual Research Report
  • [Publications] 小原一男: "血管平滑筋の伸展刺激誘発収縮について." 第6回単離平滑筋細胞研究会 講演要旨集. 6-9 (1995)

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      1997 Annual Research Report
  • [Publications] 秋丸真司: "ラットにおける皮膚循環の薬理学特性とprostaglandin E1製剤の作用について." 第93回日本薬理学会関東部会 要旨集. 49 (1995)

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      1997 Annual Research Report
  • [Publications] 湯山弘法: "単離ラット膵ランゲルハンス氏島β細胞内遊離Ca^<2+>濃度に対するNO-cGMP系活性化の影響." 第93回日本薬理学会関東部会 要旨集. 85 (1995)

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      1997 Annual Research Report
  • [Publications] 小原一男: "イヌ脳底動脈における緩徐伸展刺激誘発性収縮について." 第42回中部日本生理学会 予稿集. 21 (1995)

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      1997 Annual Research Report
  • [Publications] 田辺由幸: "膜結合型TNF前駆体による、THP-1細胞のLPS感受性の正負の制御." 第18回日本分子生物学会年会 講演要旨集. 305 (1995)

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      1997 Annual Research Report
  • [Publications] 河内千恵: "TNF3'-UTRポリAシグナル部分によるTNFの発現制御について." 第18回日本分子生物学会年会 講演要旨集. 380 (1995)

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      1997 Annual Research Report
  • [Publications] 中山貢一: "ストレッチによる血管収縮機能発現とチロシンキナーゼの特異的関与について." 平成7年度-平成8年度 文部省科学研究費補助金研究成果報告書基礎研究C(07672370). (1997)

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      1997 Annual Research Report
  • [Publications] 中山貢一: "ストレッチによる血管収縮機能発現とチロシンキナーゼの特異的関与について" 平成8年度科学研究費補助金(基礎研究C07672370)研究成果報告書. (1996)

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      1997 Annual Research Report
  • [Publications] 中山貢一: "人体機能生理学 第3版" 南江堂, 622 (1996)

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      1997 Annual Research Report
  • [Publications] 中山貢一: "薬理学" 広川書店, 1319 (1996)

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      1997 Annual Research Report
  • [Publications] Yoshio Tanaka, Tohru Nakazawa, Hiromi Ishiro, Michiyasu Saito, Kunio Ushii and Koichi Nakayama.: "Ca^<2+> handing mechanisms underlying neuropeptide Y-induced contraction in canine cerebral artery." Eur. J. Pharmacol. Mol. Sec.289. 59-66 (1995.)

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      1996 Annual Research Report
  • [Publications] Yoshio Tanaka, Tohru Nakazawa, Hiromi Ishiro, Michiyasu Saito, Kunio Ushii and Koichi Nakayama.: "Potentiation by endothelin-1 of Ca^<2+> sensitivity of contractile elements depends on Ca^<2+> influx through L-type Ca^<2+> channels in the canine cerebral artery." Gen. Pharmacol.26. 855-864 (1995.)

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      1996 Annual Research Report
  • [Publications] Hisayuki Uneyama, Yoshio Tanaka, Seinosuke Iwata, Tsuneo Ishiguro and Koichi Nakayama.: "Pharmacological chatacteristics of the canine cerebrovascular constriction produced by neuropeptide Y." Biol. Pharmaceuti. Bull.18. 501-506 (1995.)

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      1996 Annual Research Report
  • [Publications] Koichi Nakayama. Tohru Nakazawa, Yoshihisa Fukuta, and Yoshio Tanaka.: "Stereo-selective calcium antagonistic and binding properties of the enantioments of lemildipine in vascular tissue of pigs and dogs." Arzneim. Forsch./Drugs Res.46 (II). 1045-1053 (1996.)

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      1996 Annual Research Report
  • [Publications] Koichi Nakayama.: "Pharmacological profile and therapeutic perspectives of semotiadil fumarate (SD-3211), a novel benzothiazine Ca^<2+> antagonist. Cardiovasc." Drug. Rev.14. 97-134 (1996.)

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      1996 Annual Research Report
  • [Publications] Naohiro Masumoto, Koichi Nakayama, Akihiro Oyabe, Mayumi Uchino, Kunio Ishii, Kazuo Obara and Yoshiyuki Tanabe.: "Specific attenuation of the pressure-induced contraction of rat cerebral artery by herbimycin A." Eur. J. Pharmacol.(in press.).

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      1996 Annual Research Report
  • [Publications] Koichi Nakayama, Kiichiro Ueta, Yoshio Tanaka, Yoshiyuki Tanabe & Kunio Ishii.: "Stretch-unduced contraction of isolated rabiit pulmonary artery is produced by endothelium-derived thromboxane A2." Brit. J. Pharmacol.(in press.).

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      1996 Annual Research Report
  • [Publications] Tsutomu Nakahara, Kunio Ishii, Yoshio Tanaka, and Koichi Nakayama.: "Flow regulates vasodilator responses to acetylcholine in the isolated canine mesenteric arterial bed." Biol. Pharmacol. Bull.(in press.).

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      1996 Annual Research Report
  • [Publications] Tsutomu Nakahara, Kunio Ishii, Yoshio Tanaka, and Koichi Nakayama.: "Flow-dependent regulation of NO formation in the isolated canine mesenteric arterial bed." Japan. J. Pharmacol.(in press.).

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      1996 Annual Research Report
  • [Publications] K. Sako, Y. Yonemasu, M. Tsutiya, T. Asano.: "HA 1077 : a novel intrecellular calcium antagonist. 1. Pharmacology." CNS Drug Reviews. 2 (2). 160-174 (1996.)

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      1996 Annual Research Report
  • [Publications] S. Satoh, I. Ikegaki, Y. Suzuki, T. Asano, M. Shibuya, H. Hidaka.: "Neuroprotective properties of a protein kinase inhibitor against ischaemia-induced neuronal damage in rats and gerbils." Br. J. Pharmacol.118. 1592-1596 (1996.)

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      1996 Annual Research Report
  • [Publications] 生垣一郎,佐藤多恵、佐多美奈子、浅野敏雄: "蛋白リン酸化酵素阻害剤ファスジル(AT877)の血液凝固時間および血小板凝集に対する作用" 薬理と治療. 24 (4). 121-123 (1996.)

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      1996 Annual Research Report
  • [Publications] Tsutomu Nakahara, Kunio Ishii, Ken-Ichiro Iwamoto and Koichi Nakayama.: "Differential significance of nitric oxide in hypotensive mechanisms of acetylcholine and histamine in dogs." Res. Commun. Mol. Path. Pharmacol.89. 77-84 (1995.)

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      1996 Annual Research Report
  • [Publications] Tsutomu Nakahara, Kunio Ishii, Yoshio Tanaka and Koichi Nakayama.: "Involvement of neurohumoral factors in the pressor mechanism of N^G-nitro-L-arginine" Eur. J. Pharmacol.287. 49-56 (1995.)

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      1996 Annual Research Report
  • [Publications] Tsutomu Nakahara, Kunio Ishii, Yoshio Tanaka and Koichi Nakayama.: "Infusions of pressor agents selectively attenuate depressor responses to ACh in anesthetized dogs." Am. J. Physiol.271 (Heart Ciec. Physiol. 40). H273-H281 (1996.)

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      1996 Annual Research Report
  • [Publications] 竹石桂一: "白血病細胞の分化誘導時における細胞増殖必須遺伝子の発現抑制機構の解析" 薬学の進歩. 12. 107-115 (1996.)

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      1996 Annual Research Report
  • [Publications] M. Wakabayashi, H. Katai, N. Horie, K. Takeishi.: "Clonong of the monkey thymidylate synthase gene and characterization of regulatory sequences in the promoter region" Nucleic Acids Symp. Series. No.35. 227-228 (1996.)

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      1996 Annual Research Report
  • [Publications] Nobuaki Horie and Kiichi Takeishi.: "Identification of functional elements in the promoter region of the human gene for thymidylate synthase and nuclear factors that regulate the expression of the gene." J. Biol. Chem., resubmitted after revision.(1997.)

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      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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