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1987 Fiscal Year Final Research Report Summary

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
KeywordsThin-fiber muscular afferent / Polymodal receptor / Respiratory suppression Proglumide / Enkephalin / ELISA / Opioid / 結合腕傍核 / オピオイド
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.

  • Research Products

    (28 results)

All Other

All Publications (28 results)

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

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  • [Publications] 熊澤 孝朗: 医学・あゆみ. 138. 565-570 (1986)

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  • [Publications] E.Tadaki: Environ. Med.30. 47-53 (1986)

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  • [Publications] K.Mizumura: Pflugers Arch. Eur. J. Physiol.408. 565-572 (1987)

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  • [Publications] K.Eguchi: Pflugers Arch. Eur. J. Physiol.409. 367-373 (1987)

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  • [Publications] Y.Kozaki: Environ. Med.31. 55-60 (1987)

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  • [Publications] D.Simbulan: Environ. Med.31. 61-67 (1987)

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  • [Publications] 只木 英子: 環研年報. 38. 137-140 (1987)

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  • [Publications] 小崎 康子: 環研年報. 38. 141-143 (1987)

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  • [Publications] T.Kumazawa: J.Neurophysiol.57. 702-711 (1987)

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  • [Publications] T.Kumazawa: Pain. 28. 255-264 (1987)

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  • [Publications] K.Mizumura: Pflugers Arch. Eur. J. Physiol.411. 27-33 (1988)

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

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      「研究成果報告書概要(和文)」より
  • [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)

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

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

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      「研究成果報告書概要(欧文)」より
  • [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)

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      「研究成果報告書概要(欧文)」より
  • [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)

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      「研究成果報告書概要(欧文)」より
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1989-03-30  

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