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Physiology and pathophysiology of drug receptor mechanisms

Research Project

Project/Area Number 01304028
Research Category

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

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

KURIYAMA Kinya  Kyoto Pref. Univ. of Med., Dept. of Pharmacol. Prof., 医学部, 教授 (20079734)

Co-Investigator(Kenkyū-buntansha) TSUCHIHASHI Yasunari  Kyoto Pref. Univ. of Med., Dept. of Pathol. Assoc. Prof., 医学部, 助教授 (50106390)
FURUKAWA Tatsuo  Fukuoka Univ. School of Med., Dept. of Pharmacol. Prof., 医学部, 教授 (60078582)
TODA Noboru  Shiga Univ. Med. Sci., Dept. of Pharmacol. Prof., 医学部, 教授 (50025590)
TAKAORI Shuji  Shimane Med. Univ., Dept. of Pharmacol. Vice Dean, 医学部, 副学長 (10025538)
KATO Ryuichi  Keio Univ. School of Med., Dept. of Pharmacol. Prof., 医学部, 教授 (40112685)
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1991: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1990: ¥4,000,000 (Direct Cost: ¥4,000,000)
KeywordsDesensitization / Cardiac receptor / Primary cultured cells / Opioid receptor / Potassium channel / Dopamine receptor / Aging / Blood vessel / 受容体の脱感作と過感作 / カリウム チャンネル / 薬物受容体 / 過感作状態 / 加齢 / 脂肪酸 / モルヒネ耐性 / 生理と病態 / 感作及び脱感作現象 / 薬物依存 / 加齢に伴う変化 / イオンチャンネル / シナプスの可塑性 / 細胞内情報媒介系
Research Abstract

Physiological and pathophysiological roles of drug receptors in various organs were investigated in this research group and the following results and conclusions were obtained. 1) Continuous exposure of primary cultured neurons to muscarinic agonists and/or antagonists induced down- and/or up-regulation of the receptor and these changes were accompanied with those in second messenger systems coupled with the receptor. 2) The membrane stabilizing effect was essential for the protecting effect of various drugs on cardiac myopathy induced by cardiac ischemia. 3) The proliferation of vascular endotherial cells, which plays an important role in the progession of arteriosclerosis, was associated with the stimulation of alpha_1-adrenoceptor by cathecholamines. 4) The development of functional tolerance to morphine was prevented by the concomitant administrations of adrenergic blockers, k-opioid receptor agonist and calcium channel blockers. 5) Potassium channel opener selectively inhibited IP_3 -induced CA^<++> release in the heart. 6) Central dopamine D_1 receptor was operated when the excess of dopamine release was induced. 7) The function of adrenergic receptors in vascular smooth muscle showed a decrease with the progression of aging, while cholinergic receptors in this tissue were not affected significantly by aging. 8) The bata-receptors in the coronary artery were mostly beta_1 type. 9) The dilatation of cerebral arteries was mediated by the increase of cGMP caused by the activation of guanylate cyclase with NO. 10) Endothelin inhibited ganglionic transmission by ganglionic stimulation of thromboxane A_2 production as well as postganglionic activation of Ca^<++> dependent K^+channel. 11) The hypothalamus possessed both subsaince P and opioid receptors which are involved in the regulation of urinary outflow.

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] S.Ohkuma: "Alterations in receptor-coupled second messenger systems at up-regulated muscarinic receptors:Analysis using primary cultured neurons" European Journal of Pharmacology. 189. 277-285 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] K.Nakamura: "Effect of lidocaine on the accumulation of non-esterified fatty acids in the ischemic rat heart" European Journal of Pharmacology. 169. 259-267 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T.Nakai: "Inhibition of nitric oxide and nitric oxide-producing vasdilators of DNA synthesis in vascular smooth muscle cells" European Journal of Pharmacology. 189. 347-353 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H.Kaneto: "Action site of adrenergic blockers to suppress the development of tolerance to morphine analgosia" Brain Research. 507. 35-39 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T.Yanagisawa: "Cytoplasmic calcium and the relaxation of canine coronary arterial smooth muscle produced by cromakalim,pinacidil and nicorandil" Br.J.Pharmacol.101. 157-165 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] N.Toda: "Beta adrenoceptor subtype in isolated human,monkey and dog epicardial coronary arteries" Journal of Pharmacology and Experimental Therapeutics. 253. 518-524 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] S. Ohkuma: "Alterations in receptor coupled second messenger systems at up-regulated muscarinic receptors : Analysis using primary cultured neurons" European Journal of Pharmacology. 189. 277-285 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] K. Nakamura: "Effect of lidocaine on the accumulation of non-esterified fatty acids in the ischemic rat heart" European Journal of Pharmacology. 169. 259-267 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Nakai: "Inhibition of nitric oxide and nitric-producing vasdilators of DNA synthesis in vascular smooth muscle cells" European Journal of Pharmacology. 189. 347-353 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Kaneto: "Action site of adrenergic blockers to suppress the development of tolerance to morphine analgosia" Brain Research. 507. 35-39 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Yanagisawa: "Cytoplasmic calcium and the relaxation of canine coronary arterial smooth muscle produced by cromakalim, pinacidil and nicorandil" Br. J. Pharmacol.101. 157-165 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] N. Toda: "Beta adrenoceptor subtype in isolated human, monkey and dog epicardial coronary arteries" Journal of Pharmacology and Experimental Therapeutics. 253. 518-524 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M.Hirouchi: "Expresion of mRNA for GABA_A receptor α1ーsubunit in mouse brain" Neurochemistry International. 19. 375-385 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Takahashi: "Role of spinal kappa opioid receptors in the blockade of the development of antinociceptive tolerance to morphine" European Journal of Pharmacology. 200. 293-297 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Okada: "An analysis of the nitrateーlike and K channel opening actions of KRN 2391 in canine coronary arterial smooth muscle" British Journal of Pharmacology. 104. 829-838 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Momiyama: "Inhibition by tolipexole,a thiazoloーazepine derivative,of dopaminergic neurons in the ventral tegmental area" Life Sciences. 49. 535-543 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] I.Takayanagi: "Effect of aging on postsynaptic α1ーadrenoceptor mechanisms in rat aorta" General Pharmacology. 22. 211-218 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Hosokawa: "Pleomorphic xanthoastrocytoma ultrastructural,immunohistochemical and DNA cytofluorometric study of a case" Cancer. 68. 853-859 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Kuriyama: "Neuroreceptor Mechanisms in Brain" Plenum Press,New York, 452 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 栗山 欣弥: "不安の基礎と臨床" Upjohn Co.,Tokyo, 125 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] I.Takayanagi;K.Kawano;K.Koike: "Effect of aging on the response of guinea pig trachea to isoprenaline." Japanese Journal of Pharmacology. 53. 356 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Y.Nasa;K.Ichikawa;Y.Abiko: "Both dーcis and 1ーcisーdiltiazem have antiーischemic action in the isolated,perfusedworking rat heart." J.Pharmacol.Exp.Ther.255. 680-689 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Nakaki;M.Nakayama;S.Yamamoto;R.Kato: "Alpha_1ーadrenergic stimulation and beta_2ーadrenergic inhibition of DNA synthesis in vascular smooth cells." Eur.J.Pharmacol.ーMol.Pharmacol.Sec.189. 347-353 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] H.Tsushima;M.Mori;T.Matsuda: "Effect of fentanyl,injected into the hypothalamic supraoptic and paraventricular nuclei in a waterーloaded and ethanolーanesthetized rat." Neuropharmacology. 29. 757-763 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Katsuragi;T.Tokunaga;S.Usune;T.Furukawa: "A possible coupling of postjunctional ATP release and transmitters'receptor stimulation in smooth muscles." Life Science. 46. 1301-1307 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Momiyama;M.Sasa;S.Takaori: "Dー2 Receptorーmediated inhibition by a substituted quinolinone derivative,7ー{3ー[4ー(2,3ーdimethylphenyl)piperazinyl)propoxy}ー2(1H)ーquinolinone (OPCー4392),of dopaminergic neurons in the ventral tegmental area." Life Science. 47. 761-769 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Kuriyama,S.Ohkuma: "Methods in Neurosciences" Academic Press (New York), 14 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Y.Ohmori,M.Hirouchi,J.Taguchi,K.Kuriyama: "Functional Coupling of the γ-Aminobutyric Acid_B Receptor with Calcium Ion Channel and GTP-Binding Protein and Its Alteration Following Solubilization of the γ-Aminobutyric Acid_B Receptor" Journal of Neurochemistry. 54. 80-85 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] T.Okamura,Y.Minami,N.Toda: "Endothelium-Dependent and -Independent Mechanisms of Action of Acetylcholine in Monkey and Dog Isolated Arteries" Pharmacology. 38. 279-288 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] K.Nakamura,K.Ichihara,Y.Abiko: "Effect of propranolol on accumulation of NEFA in the ischemic perfused rat heart" European Journal of Pharmacology. 160. 61-69 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] K.Kihara,M.Inoue,H.Kaneto: "Adrenergi Function and the Development of Analgesic Tolerance to Morphine" Japanese Journal of Pharmacology. 50. 397-401 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] M.Hara,M.Sasa,S.Takaori: "VENTRAL TEGMENTAL AREA-MEDIATED INHIBITION OF NEURONS OF THE NUCLEUS ACCUMBENS RECEIVING INPUT FROM THE PARASCICULAR NUCLEUS OF THE THALAMUS IS MEDIATED BY DOPAMINE D_1 RECEPTORS" Neuropharmacology. 28. 1203-1209 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] T.Yanagisawa,H.Hashioto,N.Taira: "Interaction of potassium channel openers and blockers in canine atrial muscle" Britich Journal Pharmacology. 97. 753-762 (1989)

    • Related Report
      1989 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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