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Pharmacological studies on the NO-dependent and -independent NANC neurotransmitters in the human and cat airway.

Research Project

Project/Area Number 08457029
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionKyusyu University

Principal Investigator

ITO Yushi  Kyushu University, Faculty of Medicine, Professor, 医学部, 教授 (80037506)

Co-Investigator(Kenkyū-buntansha) AIZAWA Hisamichi  Kyushu University, Faculty of Medicine, Assistant Professor, 医学部, 助教授 (90175711)
INOUE Ryuji  Kyushu University, Faculty of Medicine, Assistant Professor, 医学部, 助教授 (30232573)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1996: ¥6,000,000 (Direct Cost: ¥6,000,000)
KeywordsNANC relaxation / airway / NO / VIP / cAMP / cGMP / smooth muscle / 迷走神経 / 非コリン性非アドレナリン性抑制神経
Research Abstract

Neurally mediated relaxation of airway smooth muscle, in various animal species including man, is largely non-adrenergic, non-cholinergic (NANC). Although the neurotransmitter (s) responsible for the NANC relaxation in the airways have not been conclusively identified, vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) have emerged as strong candidate for this role. The present study were carried out to examine whether and to what extent NO-related compounds and VIP mediate the NANC relaxation in cat and human airway. NANC relaxation evoked by EFS in the cat peripheral airway was biphasic, comprising an initial fast followed by a second slow component and L-NAME or L-NNA selectively abolished the first component without affecting the second one. C-PTIO,a newly synthesized NO scavenger, dose-dependently suppressed the initial component and at a concentration of 10^<-4>M almost halved the amplitude of NANC relaxation. Additional application of L-NAME further reduced the C-PTIO … More resistant NANC relaxation, thereby suggesting that the initial component of the NANC relaxation is due to NO free radial itself and NO-donors. The amplitude of the L-NAME insensitive NANC relaxation showed a fade phenomenon during the first 1 hr of stimulation at an interval of every 20min. Application of VIP (10-28) , a VIP antagonist, enhanced the rate of decrease in the amplitude of L-NAME-insensitive NANC relaxation. Zaprinast, a specific PDE tupe V inhibitor, preferentially enhanced the amplitude of the firstcomponent of the NANC relaxation, and enhanced the accumulation of [cGMP] i evoked by EFS.Rolipram, a specific PDE type IV inhibitor, enhanced both the first ad second components of the NANC relaxation to a similar extent, and enhanced the accumulator of [cAMP] i, thereby indicating that NANC relaxation is associated with concomitant accumulation in both [cAMP] i and [cGMP] i. Taken together, the present study have shown that at least NO free radical itself and NO donors such as nitrosocystine, and VIP are involved as neurotransmitters in the NANC relaxation in the airway. Less

Report

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

    (20 results)

All Other

All Publications (20 results)

  • [Publications] J.Sakai: "Autoregulation of acetycholine release from vagus nerve terminals in the dog trachea." Biomedical Res.17. 205-211 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Tanaka: "The possible role of acetylcholine release from vagus nerve terminals in the dog trachea." J.Physiol.493. 785-791 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Yamada: "E1ectrophysiological characterization of a motilin agonist,GM611,on rabbit duodenal smooth muscle." Am.J.Physiol.271. G1003-G1016 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Waniishi: "Preferential potentiation by hypotonic cell swelling of muscarinic cation current guinea pig ileum." Am.J.Physiol.272. C240-C253 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Aizawa: "L-NAME-sensitive and-insensitive nonadrenergic non-cholinergic relaxation of cat airway in vivo and in vitro." Eur.Respir.J.10. 314-321 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] V.Bauer: "Hydrogen peroxide induced responses of cat tracheal smooth muscle cells." Br.J.Pharmacol.121. 867-874 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] J.Sakai: "Autoregulation of acetycholine release from vagus nerve terminals in the dog trachea." Biomedical Res.17 :. 205-211 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Tanaka: "The possible role of acetylcholine release from vagus nerve terminals in the dog trachea." J.Physiol.493 :. 785-791 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Yamada: "Electrophysiological characterization of a motilin agonist, GM611, on rabbit duodenal smooth muscle." Am.J.Physiol.271 :. G1003-G1016 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Waniishi: "Preferential potentiation by hypotonic cell swelling of muscarinic cation current in guinea pig ileum." Am.J.Physiol.272 :. C240-C253 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Aizawa: "L-NAME-sensitive and -insensitive nonadrenergic non-cholinergic relaxation of cat airway in vivo and in vitro." Eur.Respir.J.10 :. 314-321 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] V.Bauer: "Hydrogen peroxide induced responses of cat tracheal smooth muscle cells." Br.J.Pharmacol.121 :. 867-874 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] J.Sakai: "Autoregulation of acetycholine release from vagus nerve terminals in the dog trachea." Biomedical Res.17. 205-211 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Tanaka: "The possible role of acetylcholine release from vagus nerve terminals in the dog trachea." J.Physiol.493. 785-791 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Yamada: "Electrophysiological characterization of a motilin agonist,GM611,on rabbit duodenal smooth muscle." Am.J.Physiol.271. G1003-G1016 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Waniishi: "Preferential potentiation by hypotonic cell swelling of muscarinic cation current in guinea pig ileum." Am.J.Physiol.272. C240-C253 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Aizawa: "L-NAME-sensitive and -insensitive nonadrenergic non-cholinergic relaxation of cat airway in vivo and in vitro." Eur.Respir.J.10. 314-321 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] V.Bauer: "Hydrogen peroxide induced responses of cat tracheal smooth muscle cells." Br.J.Pharmacol.121. 867-874 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Tanaka: "The possible role of nitric oxide in relaxations and excitatory neuroeffector transmission in the cat airway" J.Physiol.493・3. 785-791 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Aizawa: "L-NAME-sensitive and-insensitive nonadrenergic noncholinergic relaxation of cat airway in vivo and in vitro" Eur.Respir.J.(in press). (1997)

    • Related Report
      1996 Annual Research Report

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

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