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Establishment of the pharmacological sciences to elucidate the signal transduction system.

Research Project

Project/Area Number 04304030
Research Category

Grant-in-Aid for Co-operative Research (A)

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionNagoya University

Principal Investigator

HIDAKA Hiroyoshi  Nagoya University School of Medicine, Professor, 医学部, 教授 (80100171)

Co-Investigator(Kenkyū-buntansha) SAITO Hideya  Hokkaido University School of Medicine, Professor, 医学部, 教授 (20000929)
TODA Noboru  Shiga University of Medical Science, Professor, 医学部, 教授 (50025590)
OHTSUKA Masanori  Tokyo Medical and Dental University, School of Medicine, Professor emeritus, 医学部, 名誉教授 (60013801)
KURIYAMA Kinya  Kyoto Prefectural University of Medicine, Professor, 医学部, 教授 (20079734)
ENDO Makoto  Saitama Medical School, Professor, 医学部, 教授 (50009990)
高柳 一成  東邦大学, 薬学部, 教授 (70012599)
加藤 隆一  慶応義塾大学, 医学部, 教授 (40112685)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 1994: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1993: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1992: ¥7,000,000 (Direct Cost: ¥7,000,000)
Keywordssignal transduction / intracellular message system / molecular probe / 機能探索子 / 細胞内情報伝達系 / 創薬
Research Abstract

One of the aims of this research project was to elucidate and control the mechanisms by which the intracellular second messenger systems transduce signals derived from extracellular stimuli, using specific molecular probes. The other was to create novel function-targeted probes which are useful to investigate the intracellular mechanisms. Such a pharmacological approach is undoubtedly powerful since various biological phenomena are controlled by a network of multiple intracellular messenger systems. Through three-year work under this grant, increasing number of specific molecular probes have became available, which enabled us to understand intracellular messenger systems. A good example is KN-62 and 93, specific inhibitors of Ca/calmodulin-dependent protein kinase II,which have been widely used to investigate the functions of the kinase. We also succeeded to purify the novel type of Ca/calmodulin-dependentkinase. V.We obtained evidence concerning signal transduction mechanisms by tachykinin, GABA and serotonin in neurons using pharmacological agents. Nitric oxide was demonstrated to be involved in the neural control of the brain vessel dilation.From an molecular biological approach, two types of Ca channels releasing Ca^<2+>from the intracellular store sites have been cloned. All these findings indicate that novel specific probes are desperately required for fundamental understanding of the intracellular messenger systems. Furthermore, these probes may provide a clue to create new compounds for a clinical use.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (41 results)

All Other

All Publications (41 results)

  • [Publications] H.Mochizuki: "Purification and characterization of Ca^<2+>/calmodulin-dependent protein kinase V from rat cerebrum." J.Biol.Chem.268. 9143-9147 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Oyamada: "Primary structure and distribution of ryanodine-binding protein isoforms of the bullfrog skeletal muscle." J.Biol.Chem.269. 17206-17214 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Nakayasu: "Immunoaffinity purification and characterization of γ-aminobutyric acid(GABA)_Breceptor from bovine cerebral cortex." J.Biol.Chem.268. 8658-8664 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] R.Hosoki: "Effects of RP67580,a tachykinin NK1 receptor antagonist,on a primary afferent-evoked response of ventral roots in the neonatal rat spinal cord." Br.J.Pharmacol.113. 1141-1146 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Ayajiki: "Nitric pxide mediates,and acetylcholine modulates,neurally induced relaxation of bovine cerebral arteries." Neuroscience. 54. 819-825 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Yoshioka: "Involvement of 5-hydroxytrytamin3 receptors in the initiation of pharyngeal reflex." Am.J.Physiol.266. R1652-R1658 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Mochizuki: "Purification and characterization of Ca^<2+>/calmodulin-dependentprotein kinase V from rat cerebrum." J.Biol.Chem.268. 9143-9147 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Oyamada: "Primary structure and distribution of ryanodinebinding protein isoforms of the bullfrog skeletal muscle." J.Biol.Chem.269. 17206-17214 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Nakayasu: "Immunoaffinity purification and characterization ofgamma-aminobutyric acid(GABA)_Breceptor from bovine cerebral cortex." J.Biol.Chem.268. 8658-8664 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] R.Hosoki Effects of RP67580: "a tachykinin NK1 receptor antagonist, on a primary afferent-evoked response of ventral roots in the neonatal rat spinal cord." Br.J.Pharmacol.113. 1141-1146 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Ayajiki: "Nitric pxide mediates, and acetylcholine modulates, neurally induced relaxation of bovine cerebral arteries." Neuroscience. 54. 819-825 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Yoshioka: "Involvement of 5-hydroxytrytamin3 receptrors in the initiation of pharyngeal reflex." Am.J.Physiol.266. R1652-R1658 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Minami: "The effect of KN‐62,Ca^<2+>/calmodulin dependent protein kinase II inhibitor on cell cycle." Biochem.Biophys.Res.Commun.199. 241-248 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] M.Tsukioka: "pH dependence of inositol 1,4,5‐trisphosphate‐induced Ca^<2+> release in permeabilized smooth muscle cells of the guinea+pig." J.Physiol.475. 369-375 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] S.Ohkuma: "GABA_A receptor stimulation enhances HMDA‐induced Ca^<2+>‐influx in mouse cerebral cortical neurons in primary culture." Molecular Brain Research. 27. 145-151 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Suzuki: "Involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters in neonatal rat spinal cord." Br.J.Pharmacol.113. 310-316 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] N.Toda: "Impairment by damage of the pterygopal ganglion of introxidergic vasodilator nerve function in canine cerebral and retinal arteries." Circ.Res.72. 206-213 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] M.Yoshioka: "Effects of 5‐hydroxytryptamine on glossopharyngeal afferent nerve activity in anesthetized rats." European J.Pharmacol.236. 491-494 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Mochizuki et al.: "Purification and characterization of Ca^<2+>/calmodulin-dependent protein kinase V from rat cerebrum." J.Biol.Chem.268. 9143-9147 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] H.Nakayazu et al.: "Immunoaffinity purification and characterization of gamma-aminobutyric acid (GABA)_B receptor from bovine cerebral cortex." J.Biol.Chem.268. 8658-8664 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] F.-Y.Zhao et al.: "Involvement of NK_1 receptors in synaptic transmission in the guinea pig coeliac ganglion." Neurosci.Res.18. 245-248 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Iino et al.: "Critical intracellular Ca^<2+> concentration for all-or-none Ca^<2+> spiking in single smooth muscle cells." EMBO J.12. 5287-5291 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] H.Saito et al.: "Role of serotonin receptors in the peripheral nervous system." Biogenic Amines. 10. 181-194 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Kohi et al.: "On the mechanizm of action of the beta-1 partial agonist denopamine in regulation of myocardial contractility:Effects on myocardial alpha adrenoceptors and intracellular Ca^<++> transients." J.Pharmacol.Exp.Ther.265. 1292-1300 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] R.Kurata et al.: "Eicosanoid-induced Ca^<2+> release and sustained contraction in Ca^<2+>-free media are mediated by different signal transduction pathways in rat aorta." Brit.J.Pharmacol.110. 875-881 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] F.Shintani et al.: "Interleukin-1β augments release of norepinephrine,dopamine and serotonin in the rat anterior hyopthalamus." J.Neurosci.13. 3574-3581 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Terasawa et al.: "Neurocalcin:a novel calcium-binding protein from bovine brain." Journal of Biological Chemistry. 267. 19596-19599 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Wakusawa et al.: "Overcoming of vinblastin resistance by isoquinolinesulfonamide compounds in abriamycin-resist leukemia cells." Molecular Pharmacology. 41. 1034-1038 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Oda et al.: "Five steps in leukocyte extravasation in the microcirculation by chemoattactants." Mediators of Tnflammation. 1. 403-409 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] SSJ.Mohsin et al.: "Important suppressive roles of the kallikrain-kinin system during the developmental stage of hypertension in spontaneously hypertensive rats." Asia Pacific Journal of Pharmacology. 7. 73-82 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] H.Nakayasu et al.: "Immunoaffinity purification and characterization of γ-aminobutylic acid(GABA)B receptors from bovine cerebral cortex." Journal of Biological Chemistry.

    • Related Report
      1992 Annual Research Report
  • [Publications] 栗山 欣也 ら: "モノクローナル抗体を用いたGABA受容体の免疫組織化学:GABAB受容体を中心として." 日本薬理学会誌.

    • Related Report
      1992 Annual Research Report
  • [Publications] 高柳 一成 ら: "アセチルコリン及びアドレナリン受容体機構の問題点とその検討" 日本薬理学会誌. 100. 279-292 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Satoh et al.: "Characterization of a_1-adrenoceptor subtypes labeled by [ ^3H]prazosin in single cells prepared from rabbit thoracic aorta." Europian Journal of Pharmacology. 221. 35-41 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 吉岡 充弘 ら: "末梢性セロトニン受容体と呼吸循環調節." 日本薬理学会誌. 100. 183-191 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Katano et al.: "Effects of cardiotonic quinolinone derivative Y-20487 on the isoproterenol-induced positive en otropic action and cyclic AMP acumulation in rat ventricular myocardium:comparison with rolipram,Ro20-1724,milrinone,and isobutylmethylxanthine." Journal of Cardiovascolar Pharmacology. 20. 715-722 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Kawabata et al.: "Effects of the positive inotropic agent Org 30029 on developed force and aequorin light transients in intact canine ventricular myocardium." Circular Research. 72. 597-606 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Yanagisawa et al.: "The isolated spinal cord-skin preparation of the newborn rat and effects of some algogenic and analgesic substances." Europian Journal of Pharmacology. 220. 111-117 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Yanagisawa et al.: "Enzymatic inactivation of tachykinin neurotransmitters in the isolated spinal cord of the newborn rat." Neuroscience Research. 15. 289-292 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] N.Toba et al.: "Reciprocal regulation by putatively nitroxidergic and adrenergic nerves of monkey and dog temporal arteries." American Journal of Physiology. 261. H1740-H1745 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 戸田 昇 ら: "神経伝達とNO." 日本薬理学会誌. 100. 173-182 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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