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Neuro-humoral mechanisms of relexive respiratory suppression mediated by endogenous opiated system.

Research Project

Project/Area Number 60440027
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Neurophysiology and muscle physiology
Research InstitutionRes. Inst. of Environ. Med. Nagoya Univ.

Principal Investigator

KUMAZAWA Takao  Res. Inst. of Environ. Med. Nagoya Univ. Professor, 環境医学研究所, 教授 (20022775)

Co-Investigator(Kenkyū-buntansha) EGICHI Knihiro  Sch. of Dent. Aichigakuin Univ. Assistant Professor, 歯学部, 助手 (30113062)
KITO Junzo  Sch. of Med. Nagoya Univ. Associate Professor, 医学部, 助教授 (60022802)
KOZAKI Yasuko  Res. Inst. of Environ. Med. Nagoya Univ. Research Associate, 環境医学研究所, 教務職員 (20126882)
MIZUMURA Kazue  Res. Inst. of Environ. Med. Nagoya Univ. Associate Professor, 環境医学研究所, 助教授 (00109349)
Project Period (FY) 1985 – 1987
Project Status Completed (Fiscal Year 1987)
Budget Amount *help
¥10,900,000 (Direct Cost: ¥10,900,000)
Fiscal Year 1987: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1986: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1985: ¥7,700,000 (Direct Cost: ¥7,700,000)
KeywordsThin-fiber muscular afferent / Polymodal receptor / Respiratory suppression Proglumide / Enkephalin / ELISA / Opioid / 結合腕傍核 / オピオイド / 酵素標識免疫測定法 / モルフィン / プログロマイド
Research Abstract

Our previous works have revealed naloxone-reversible respiratory suppression induced by stimulation of thin-fiber muscular afferents: polymodal receptor inputs. The present work is aimed to elucidate the following questions provided by those previous works. 1)Whether N. parabrachialis (PBN) is implicated in the respiratory inhibition, since previous decerebration experiment suggested the importance of the rostral pons. 2)What kinds of modulation factors are involved, since repeated stimulation reduced the magnitude of the respiratory inhibition. 3) What opioid peptide(s) may be really concerned. In addition the receptor characteristics of polymodal receptors are investigated in detail.
Results. 1)Both repetitive electrical stimulation of PBN and microinjection of morphine into PBN produced naloxone-reversible, long lasting respiratory supression, which is similar to that induced by peripheral muscular afferent stimulation. 2)Respiratory suppression produced by morphine did not reduce by its repetitive application, suggesting that opioid tolerance is not the cause of the tachyphylaxis of the reflex res[piratory suppression. Since the tachyphylaxis was antagonized by proglumide, an antagonist of cholecystokinin (CCK), it may be caused by a temporal summation of activities in facilitatory systems such as CCK, which would be simultaneously stimulated by muscular afferents. Effectiveness of the stimulation was shown to be respiratoy-phase dependent; influence of vagal inputs was also suggested. 3)Perfusion through the 4th ventricle-cisterna magna with solution containing enkephalinase inhibitors caused significantly larger reflex respiratory suppression. Concentration of enkephalin determined by ELISA was higher in the elute during and after stimulation than before.
The present result reveals an enkephalinergic respiratory regulation mechanism triggered by peripheral polymodal receptor inputs.

Report

(3 results)
  • 1987 Final Research Report Summary
  • 1986 Annual Research Report
  • 1985 Annual Research Report
  • Research Products

    (43 results)

All Other

All Publications (43 results)

  • [Publications] 小崎 康子: 環研年報. 37. 169-170 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 熊澤 孝朗: 医学・あゆみ. 138. 565-570 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] E.Tadaki: Environ. Med.30. 47-53 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] K.Mizumura: Pflugers Arch. Eur. J. Physiol.408. 565-572 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] K.Eguchi: Pflugers Arch. Eur. J. Physiol.409. 367-373 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Y.Kozaki: Environ. Med.31. 55-60 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] D.Simbulan: Environ. Med.31. 61-67 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 只木 英子: 環研年報. 38. 137-140 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 小崎 康子: 環研年報. 38. 141-143 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] T.Kumazawa: J.Neurophysiol.57. 702-711 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] T.Kumazawa: Pain. 28. 255-264 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] K.Mizumura: Pflugers Arch. Eur. J. Physiol.411. 27-33 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] T.Kumazawa: "Sensory Innervation of reproductive organs. Visceral Sensation, Progress in Brain Res. Vol. 67" Elsevier, Amsterdam, PP.115-131 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] T.Kumazawa: "Modulations of testicular polymodal receptor activity: Implication of receptors in inflammatory pain in Fine Afferent Nerve Fibers and Pain." VCH Verlagsgesellschaft mbh, Weiheim, PP.147-157 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Y. Kozaki: "Determination of met-enkephalin in cerebrospinal fluid (Preliminary report)." Ann. Res. Inst. Environ. Med. Nagoya Univ.37. 169-170 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] T. Kumazawa: "Pain as the bio-alarm signal-defense system" Igaku no Ayumi. 138. 565-570 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] E. Tadaki: "Effects of proglumide, a cholecystokinin antagonists, on opiate-mediated respiratory suppression induced by thin-fiber muscular afferent." Environ. Med.30. 47-53 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] K. Mizumura: "Effects of prostanglandins and other putative chemical intermediaries on the activity of canine testicular polymodal receptors studied in vitro." Pflugers Arch.-Eur. J. Physiol.409. 565-572 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] K. Eguchi: "Respiratory depression caused by either morphine microinjection or repetitive electrical stimulation in the region of the nucleus parabrachialis of cats." Pflugers Arch.- Eur. J. Physiol.409. 367-373 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Y. Kozaki: "Effects of enkephalinase inhibitors on reflex respiratory suppression induced by thin-fiber muscular afferents." Environ. Med.31. 55-60 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] D. Simbulan: "Phrenic responses to muscle afferent nerve stimulation applied to different respiratory phases." Environ. Med.31. 61-67 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] E. Tadaki: "Excitatory and inhibitory respiratory responses to morphine in cats." Ann. Res. Inst. Environ. Med. Nagoya Univ.38. 137-140 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Y. Kozaki: "Modulation influences by enkephalinase inhibitors on reflex respiratory suppression induced by thin-fiber muscular afferents." Ann. Res. Inst. Environ Med. Nagoya Univ.38. 141-143 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] T. Kumazawa: "Response properties of polymodal receptors studied using in vitro in vitro testis superior spermatic nerve preparations of dogs." J. Neurophysiol.57. 702-711 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] T. Kumazawa: "Thermally potentiated respones to algesic substances of visceral nociceptors." Pain. 28. 255-264 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] K. Mizumura: "Respiratory changes induced by activation of testicular afferents in dogs." Pflugers Arch. - Eur. J. Physiol.411. 27-33 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] T. Kumazawa: Sensory Innervation of reproductive organs. Visceral Sensation, Progress in Brain Res. Vol. 67. Elsevier, Amsterdam., pp.115-131 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] T. Kumazawa: Modulations of testicular polymodal receptor activity : Implication of receptors in inflammatory pain.in Fine Afferent Nerve Fibers and Pain.VCHVerlagsgesellschaft mbH, Weiheim., pp.147-157 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 只木英子: 環境医学研究所年報. 37. 159-162 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 江口国博: 環境医学研究所年報. 37. 163-168 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 小崎康子: 環境医学研究所年報. 37. 169-170 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Y.Takesue: Neurochemical reseaech. 11. 147 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] E.Tadaki: 日本生理学雑誌. 48. 381 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] K.Eguchi: 日本生理学雑誌. 48. 383 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 小崎康子: 環境医学研究所年報. 38. (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] 只木英子: 環境医学研究所年報. 38. (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] 小崎康子: 日本生理学雑誌. 49. (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] K.Eguchi: Pfl【u!‥】gers Archiv.

    • Related Report
      1986 Annual Research Report
  • [Publications] 第7回日本疼痛学会プログラム・口演要旨集. (1985)

    • Related Report
      1985 Annual Research Report
  • [Publications] 日本生理学雑誌. 48-1. (1986)

    • Related Report
      1985 Annual Research Report
  • [Publications] 日本生理学雑誌. 48-2,3. (1986)

    • Related Report
      1985 Annual Research Report
  • [Publications] 日本生理学雑誌. 48-2,3. (1986)

    • Related Report
      1985 Annual Research Report
  • [Publications] 環研年報. 37. (1986)

    • Related Report
      1985 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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