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Molecular Pharmacology of Selective beta3-Adrenergic Receptors

Research Project

Project/Area Number 07557327
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field General pharmacology
Research InstitutionTohoku University

Principal Investigator

YANAGISAWA Teruyuki  Tohoku University, Sch.Med., Dept.Pharmacol., Professor, 医学部, 教授 (90133941)

Co-Investigator(Kenkyū-buntansha) KUROSAWA Hideo  Tanabe Seiyaku, Biol.Res.Lab., 医薬育成研究所, 主任研究員
YAMADA Hiroaki  Nisshin Flour Milling, Pharmaceutical Res.Lab., 生物研究所, 主任研究員
SATO Yasufumi  Tohoku University, Inst.Aging & Development, Professor, 加齢医学研究所, 教授 (50178779)
SUKEGAWA Jun  Tohoku University, Sch.Med., Dept.Pharmacol., Lecturer, 医学部, 講師 (30187687)
NUNOKI Kazuo  Tohoku University, Sch.Med., Dept.Pharmacol., Lecturer, 医学部, 講師 (10172743)
山田 博幸  日清製粉, 生物研, 主任研究員
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1996: ¥3,500,000 (Direct Cost: ¥3,500,000)
Keywordsatypical beta-Adrenoceptors / beta3-Adrenoceptor / isoproterenol / BRL37344 / beta1-Adrenoceptor / beta2-Adrenoceptor / Antiobesity / 遺伝子 / Iodocyanopindolol / β_3受容体 / β_1受容体 / イソブロテレノール / 脂肪細胞 / クローン細胞 / サイクリ.ク AMP / 結合実験 / β_2受容体 / 心筋
Research Abstract

In isolated canine right ventricular muscles, we investigated the differences in antagonisms by beta-blockers against the positive inotropic effects (PIEs) of isoproterenol, a nonselective agonist, and T-0509, a beta1-selective agonist. The selective beta1-blockers atenolol or bisoprolol, and nadolol, a nonselective beta-blocker antagonized the PIE of T-0509 monophasically in Schild analysis, showing pA2 values of 7.05,7.63, and 7.58, respectively. On the other hand, both blockers produced biphasic antagonism against the PIE of isoproterenol (ISO) ; therefore, two pKB values were obtained (7.75 and 4.25 ; 7.82 and 5.76 ; 7.42 and 4.39, respectively). Because the different mode of antagonism by three beta-blockers between T-0509 and ISO could not be explained by the selectivities of beta-agonists and blockers for beta1- and beta2-adrenoceptors in the heart, two subtypes of beta1-adrenoceptors may exist together in canine ventricular muscles, and atenolol, bisoprolol, and nadolol may act as antagonists for the two subtypes (beta1- and atypical beta- or beta3-adrenoceptors) with two different affinities.
The influences were investigated of denopamine, beta1-adrenoceptor partial agonist, on the life span of cardiomyopathic hamsters (BIO 14.6 strain) in the heart failure period. The survival rate of denopamine group at 65 weeks of age was higher than control group. Denopamine treatment lowered plasma levels of noradrenaline and dopamine (P < 0.05), but affected neither the cardiac contractility nor the beta-adrenoceptor density. In summary, denopamine significantly decreases the mortality of cardiomyopathic hamsters. Its effect to lower the plasma catecholamine levels may be responsible for the beneficial effect of denopamine.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (39 results)

All Other

All Publications (39 results)

  • [Publications] KuroxawaH, YanagisawaT, TairaN: "Biphasic antagonisms of β-blockers aginst positive inotropic response via β_1 adrenoceptors in isolated canine right ventricular muscles:" J.Cardiovasc.Pharmacol.27.1. 262-268 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 柳澤 輝行: "血管平滑筋のK^+チャネル" 血管と内皮,. 6・3. 221-231 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Murakoshi, H., Nunoki, K.et al.: "Determinateon of K_A values by controlled receptor expression in Xenopus oocytes." Br.J.Pharmacol.116. 2062-2066 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] KurosawaH.NaritaH.et al.: "Prolongation of the life span of cardiomyopathic Hamster by the adrenergic β 1-selective partial agonis denopamine." JpnJ.Pharmacol.72・4. 325-333 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 柳澤 輝行: "Caセンシタイザー.特集「心臓の機能とカルシウム」" Clinical Calcium. 6・9. 1114-1117 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] SugaiK, YanagisawaT., et al: "Levcromiakalim deeereases cytopalasimic Ca^<2+>,vasculas tore and Ca^<2C> senstivity in canine basilan artery" Fund.Clin.Pharmacol. (in pross). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Teruyuki, Yanagisawa:"In “Molecular and Cellular Mechanisms of Cardivascular Regulation" pp.183-193,1996,ed.by. by M. Endoh,H,Scholtz,M.Morad & T.Ilijima,Springer-Verlag,Tokyo." Hyperpolarization-relaxation coupling in vascular smooth muscle:Findgs with K^+ channel openers., 11 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 柳澤 輝行: "新薬理学入門" 南山堂, 372 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hitoshi OKADA,Kuniaki ISHII,Kazuo NUNOKI & Norio TAIRA: "Cloning of a swelling-induced chloride current related protein from rabbit heart." Biochim.Biophys.Acta.1234. 145-148 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masaaki KAGEYAMA,Teruyuki YANAGISAWA & Norio TAIRA: "Effects of semotiadil fumarate, a novel Ca^<2+> antagonist, on cytosolic Ca^<2+> level and force of contraction in porcine coronary arteries." Br.J.Pharmacol.114 (6). 1289-1295 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hideyuki MURAKOSHI,Kazuo NUNOKI,Kuniaki.ISHII & Norio TAIRA: "Determination of K_A values by controlled receptor expression in Xenopus oocytes." Br.J.Pharmacol.116. 2062-2066 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hideo KUROSAWA,Teruyuki YANAGISAWA & Norio TAIRA: "Biphasic antagonisms of beta-blockers against positive inotropic response via beta1 adrenoceptors in isolated canine right ventricular muscles : possible involvement of two beta1 adrenoceptor subtypes." J.Cardiovasc.Pharmacol.27 (1). 262-268 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshiteru SASAKI,Kuniaki ISHII,Kazuo NUNOKI,YAMAGISHI T.& Norio TAIRA: "Voltage-dependent K^+ channel (Kv1.5) cloned from rabbit heart and facilitation of inactivation of the delayd rectifier current by the rat beta subunit." FEBS Lett. 372. 20-24 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Chika IWASAKA., Katuhiro TANAKA,Manami ABE & Yasufumi SATO: "Ets-1 regulates angiogenesis by inducing the expression of urokinase-type plasminogen activator and matrix metalloproteinase-1 and the migration of vascular endothelial cells." J.Cell.Physiol. 169 (3). 522-531 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yuzuru OHUCHI,Kazuhiko YANAI,Eiko Sakurai, Hiroyuki FFUKUI,Teruyuki YANAGISAWA & Takehiko Watanabe: "Histamine-induced calcium mobilization in single cultured cells expressing histamine H1 receptors : A relationship between its sensitivity and the density of H1 receptors." Intern.J.Mol.Med.1. 355-360 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kazuyuki SUGAI,Teruyuki YANAGISAWA,Osamu MOTOHASHI,Michiyasu SUZUKI &Takashi YOSHIMOTO: "Levcromakalim decreases cytoplasmic Ca^<2+>, vascular tone and Ca^<2+> sensitivity in canine basilar artery." Fund.Clin.Pharmacol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Teruyuki YANAGISAWA: Hyperpolarization-relaxation coupling in vascular smooth muscle : Findings with K^+ channel openers. (In "Molecular and Cellular Mechanisms of Cardiovascular Regulation" ). Springer-Verlag, Tokyo., 183-193 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ohuchi Y, et al: "Histamine-induced calcium mobilization in single cultured cells expressing histamine Hl receptors:A relationship between its sensitivity and the density of Hl receptors." Intern.J.Mol.Med.1. 355-360 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sugai K.et al.: "Levcromakalim decreases cytoplasmic Ca^<2+>,vascular tone and Ca^<2+>sensitivity in canine basilar artery." Fund.Clin.Pharmacol.in press. (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 柳澤輝行 他: "カルシウム拮抗薬はなぜ効くか? カルシウム拮抗薬の分子・細胞薬理学.特集「カルシウム拮抗薬の新潮流」" Clinical Calcium. 7(12). 1593-1600 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 柳澤輝行: "血管のKチャネル.その1 K_<ir>とK_<ATP>の分子薬理学." 血管と内皮. 8(1). 82-86 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 柳澤輝行、布木和夫: "血管のKチャネル.その2 K_<Ca>とK_Vの分子薬理学." 血管と内皮. 8(2)(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 柳澤輝行、布木和夫、清水雅行: "カルシウム拮抗薬の分子薬理学.特集「高血圧の分子医学」" 現代医療. 30(4)(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 柳澤輝行: "新薬理学入門" 南山堂, 372 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 柳澤輝行: "高血圧を識る(K^+チャネルオープナ-)" 文光堂, 3 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kunosawa H, Yanagisawa T, Taira N: "Biphasic antagonisms of β-blockers against positive inotropic response via β_1 adrenoceptors in isolated canine right ventricular muscles :" J. Cardiovasc. Pharmacol.27.1. 262-268 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 柳澤輝行: "血管平滑筋のK^+チャネル." 血管と内皮,6(3) 221-231,1996.6・3. 221-231 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 柳澤輝行: "カリウムチャネルブロッカーとオープナ-." 循環制御,17(2) 180-188,1996.17・2. 180-188 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 柳澤輝行・須貝和幸: "K^+チャネルと血管平滑筋." 脳神経外科速報,6(8) 585-589,1996.6・8. 585-589 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 柳澤輝行: "Caセンシタイザー.特集「心臓の機能とカルシウム」" Clinical Calcium 6(9), 1114-1117, 1996.6・9. 1114-1117 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Teruyuki YANAGISAWA :"In "Molecular and Cellular Mechanisms of Cardiovascular Regulation" pp. 183-193, 1996. ed. by M. Endoh, H, Scholtz. M. Morad & T. Iijima, Springer-Verlag. Tokyo." Hyperpolarization-relacation coupling in vascular smooth muscle : Findings with K^+ channel openers., 11 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kageyama M,Yanagisawa T, Taira N: "Effets of sematin dil fumarcte, a norel Ca^<2+>antyonist, on cytosohc Ca^<2+>level and force of contraction in porcine coronary artery." Brit J. Phavmaiol.114. 1289-1295 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Okada Y., Yanagisawa T.: "Membrane potmticl regnletes the Ca^<2+>pensitivity of contra tile elements in coronary arterial smooth muscle." Heart Vessels. Suppl.9. 150-152 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kurosawa H, Yanagisawa T, Taira N: "Biphacic antrgonisms of β-blocrers against positive introgic resporsa via β_1 adrenouptors in isolated cative right venitricnlav muscle." J. Cardiovasc. Pharmacol.27. 262-268 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 柳澤輝行: "Caチャネル作動薬の新しい動向" 循環器科. 37. 325-333 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 柳澤輝行: "Ca拮抗薬の種類と特徴" Clinical Calcium. 5. 840-846 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 柳澤輝行: "カリウムチャネルと過分極弛緩達関" 日薬雑誌. 106. 157-169 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yanagisawa T.: "Molecular and Cellnlar Mechanisms of Cardiovasculan Regnlation" Springer-Verlag,Tokyo(in press), 11 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 柳澤輝行: "カルシウム拮抗薬-解明された基礎と臨床への応用-" 医薬ジャーナル社, 300(15) (1995)

    • Related Report
      1995 Annual Research Report

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

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