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Study for the effects of neuroactive peptides newly isolated

Research Project

Project/Area Number 04044075
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionGifu University

Principal Investigator

TAKEUCHI Hiroshi  Department of Physiology, Gifu University School of Medicine, 医学部, 教授 (10033333)

Co-Investigator(Kenkyū-buntansha) APORTADERA Luisa l.  Department of Internal Medicine, Davao Medical School Foundation, 助教授
DE la Cruz H  ダバオ医科大学, 教授
VICENTE Warlito c.  Department of Surgery, Davao Medical School Foundation, 助教授
PAGULAYAN Im  フィリピン大学, 理学部, 教授
LASTIMOSA Hi  フィリピン大学, 理学部, 教授
SIN Ramon l.  Department of Pathology, Faculty of Medicine and Surgery, University of Santo To, 医学部, 教授
TORRALBA Tito p.  Department of Internal Medicine, Faculty of Medicine and Surgery, University of, 医学部, 教授
SEVILLA Fortunato  Research Center for the Natural Science, University of Santo Tomas, 理学部, 教授
DAYAO Virginia f.  Department of Biological Sciences, College of Science, University of Santo Tomas, 理学部, 教授
KANAPI Carmen g.  Department of Biological Sciences, College of Science, University of Santo Tomas, 理学部, 教授
MUNEKATA Eisuke  Institute of Applied Biochemistry, University of Tsukuba, 応用生物化学系, 教授 (60072766)
MAMO Tadaaki  Research Institute of Environmental Medicine, Nagoya University, 環境医学研究所, 教授 (30023659)
DEURA Shigeyuki  Department of Anatomy, Fujita Health University School of Medicine, 医学部, 教授 (40021448)
MORI Akitane  Department of Neurochemistry, Institute for Neurobiology, Okayama University Med, 医学部, 教授 (20028434)
YAMAMOTO Noriko  College of Sciences, Gifu University, 医療技術短期大学部, 教授 (70021409)
ARAKI Yoko  Department of Physiology, Gifu University School of Medicine, 医学部, 助手 (20176374)
LEE Ken  Department of Physiology, Gifu University School of Medicine, 医学部, 助教授 (00212316)
PAGULAYAN Imelda f.  Institute of Biology, College of Science, University of the Philippines
LASTIMOSA Hilda d.  Department of Biological Sciences, Cebu College, University of the Phylippines
DE LA CRUZ Honorio e.  Department of Pediatrics, Davao Medical School Foundation
LUISA L.Apor  ダバオ医科大学, 助教授
HONORIO de l  ダバオ医科大学, 教授
WARLITO C.Vi  ダバオ医科大学, 助教授
RAMON L.Sin  サントトマス大学, 医学部, 教授
TITO P.Torra  サントトマス大学, 医学部, 教授
VIRGINIA F.D  サントトマス大学, 理学部, 教授
FORTUNATO Se  サントトマス大学, 理学部, 教授
CARMEN G.Kan  サントトマス大学, 理学部, 教授
有吉 安男  味の素(株), 中央研究所, 参与
宗岡 洋二郎  広島大学, 総合科学部, 教授 (40031330)
LUISA L Apor  ダバオ医科大学, 助教授
WARLITO C Vi  ダバオ医科大学, 助教授
RAMON L Sin  サントトマス大学, 医学部, 教授
TITO P Torra  サントトマス大学, 医学部, 教授
EUSTACIA M R  サントトマス大学, 医学部, 教授
VIRGINIA F D  サントトマス大学, 理学部, 教授
CARMEN G Kan  サントトマス大学, 理学部, 教授
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1992: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsNeuroactive peptides / Achatin-I / D-Amino acid residue / Neurotransmitter / Neuromodulator / Intracellular signal transduction system / Molluscan giant neurones / African giant snail (Achatina fulica Ferussac) / 神経ペプチド / 興奮性神経伝達物質 / 巨大神経細胞 / 軟体動物 / フィリピン / ペプチド / 抑制性神経伝達物質 / APGW-amide
Research Abstract

This year, we studied comprehensively effects of biologically-active peptides on the identifiable giant neurones of an African giant snail (Achatina fulica Ferussac) by the electrophysiological methods. The Achatina giant neurones were insensitive to the mammalian neurotransmitter peptides, such as substance P,Met-enkephalin, neurotensin, etc., except for oxytocin. On the other hand, these neurones were sensitive to the neuroactive peptides isolated from invertebrates. These findings were different from those of small molecule putative neurotransmitters, such as dopamine, serotonin and GABA.With these results, it was considered that one peptide neurotransmitter acts on the neurones of the less extent of animal species than the small molecule putative neurotransmitter. Achatina giant neurones were excited by achatin-I (Gly-D-Phe-Ala-Asp), isolated from Achatina ganglia by the collaboration of us, Suntory Institute for Bioorganic Research and University of Santo Tomas. APGW-amide (Ala-Pr … More o-Gly-Trp-NH_2), isolated also from Achatina ganglia by us, were inhibited Achatina giant neurones. These two peptides were proposed to be neurotransmitters for Achatina neurones. Besides, we demonstrated that Achatina cardio-excitatory peptide-1 (ACEP-1) (Ser-Gly-Gln-Ser-Trp-Arg-Pro-Gln-Gly-Arg-Phe-NH_2) isolated from Achatina ganglia by another group showed excitatory effects on Achatina giant neurones, and that fulicin (Phe-D-Asn-Gln-Phe-Val-NH_2) isolated from Achatina ganglia by another group had inhibitory effects on these neurones. We demonstrated also that FMRFFamide (Phe-Met-Arg-Phe-NH_2) isolated from the clam ganglia, AF1 (Lys-Asn-Glu-Phe-Ile-Arg-phe-NH_2), a related compound of FMRFamide isolated from an Ascaris, and [Ser^2]-Mytilus inhibitory peptide ([Ser^2]-MIP) (Gly-Ser-Pro-Met-Phe-Val-NH_2) isolated from Mytilus, had inhibitory effects on these neurones.
The intracellular signal transduction systems for the excitatory effects of achatin-I and the inhibitory effects of fulicin were studied electrophysiologically using the inhibitors for these systems. H-89 (protein kinase (PK) A inhibitor) and W-7 (calmodulin inhibitor) inhibited the achatin-I effects, and IBMX (cyclic AMP phosphodiesterase inhibitor) facilitated the same effects, indicating that achatin-I acted via cyclic AMP-PKA system, and calmodulin participated in this system. On the other hand, KT-5823 (PKG inhibitor), calphostin C (PKC inhibitor) and W-7 suppressed the inhibitory effects of fulicin, indicating that fulicin acted via cyclic GMP-PKG system and/or IP_3 and DG-PKC systems, and calmodulin participated in these systems. IBMX suppressed the inhibitory effects, the mechanism of which cannot be explained at present.
We demonstrated that APGW-amide, as well as achatin-I,acted not only as a neurotransmitter but also as a neuromodulator for Achatina neurones. Less

Report

(3 results)
  • 1994 Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Takeuchi H.,Liu G.J.,Hosoki K.and Karasawa T.: "Pharmacological characteristics of Monatepil maleate(AJ-2615),a novel structure Ca^<2+>-entry blocker,with antihypertensive,antiatherosclerotic,α_1-adrenoceptor antagonistic,and antidyslipidemic effects." Cardiovasc.Drug Rev.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Santos D.E.,Liu G.J.and Takeuchi H.: "Blockers for excitatory effects of achatin-I,a tetrapeptide having a D-phenylalanine residue,on a snail neurone." European J.Pharmacol.272. 231-239 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Emaduddin M.,Liu G.J.and Takeuchi,H.: "Pharmacological features of dopamine receptors in snail neurones." European J.Pharmacology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Liu G.J.and Takeuchi H.: "Suppressing effects of neuroactive peptides on the inward current caused by achatin-I,an Achatina endogenous peptide." Gen.Pharmacl.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Araki Y.,Liu G.J.,Zhang W.,Takeuchi H.and Munekata E.: "Further mapping of the Achatina giant neurone types sensitive to the neuroactive peptides isolated from invertebrates." Gen.Pharmacol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeuchi H.,Araki Y.,Emaduddin M.,Zhang W.,Han X.Y.,Salunga T.L.and Wong S.M.: "Identifiable giant neurones:their localizations in ganglia,axonal pathways and pharmacological features." Gen.Pharmacol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] ムハンマド・エマドゥディン,劉 国君,韓 暁燕,竹内 宏: "Achatina fulica巨大神経細胞に対するカテコールアミンの作用." 神経化学. 33. 652-653 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 張 唯,荒木陽子,ツキジデス・L・サルンガ,竹内 宏: "Achatina fulica巨大神経細胞に対するL-グルタミン酸関連物質の作用." 神経化学. 33. 650-651 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 劉 国君,翁 述民,竹内 宏: "神経ペプチドによるachatin-I興奮作用の修飾." 神経化学. 33. 648-649 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeuchi H.,Liu G.J.,Kim K.H.,Santos D.E.,Emaduddin M.,Zhang W.and Araki Y.: "Environment and Physiology" Narosa Publishing House, (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeuchi H., Liu G.J., Hosoki K.and Karasawa T.: "Pharmacological characteristics of Monatepil maleate (AJ-2615), a novel structure Ca^<2+>-entry blocker, with antihypertensive, antiatherosclerotic, alpha_1-adrenoceptor antagonistic, and antidyslipidemic effects." Cardiovasc.Drug Rev.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Santos D.E., Liu G.J.and Takeuchi H.: "Blockers for excitatory effects of achatin-I,a tetrapeptide having a D-phenylalanine residue, on a snail neurone." European J.Pharmacol.272. 231-239 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Emaduddin M., Liu G.J.and Takeuchi, H.: "Pharmacological features of dopamine receptors in snail neurones." European J.Pharmacology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Liu G.J.and Takeuchi H.: "Suppressing effects of neuroactive peptides on the inward current caused by achatin-I,an Achatina endogenous peptide." Gen.Pharmacl.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Araki Y., Liu G.J., Zhang W., Takeuchi H.and Munekata E.: "Further mapping of the Achatina giant neurone types sensitive to the neuroactive peptides isolated from invertebrates." Gen.Pharmacol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeuchi H., Araki Y., Emaduddin M., Zhang W., Han X.Y., Salunga T.L.and Wong S.M.: "Identifiable giant neurones : their localizations in ganglia, axonal pathways and pharmacological features." Gen.Pharmacol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeuchi H., Liu G.J., Kim K.H., Santos D.E., Emaduddin M., Zhang W.and Araki Y.: Narosa Publishing House. Environment and Physiology, 41-53 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Liu G.J.and Takeuchi H.: "Modulatory effects of achatin-I,an Achatina endogenous neuroactive peptides,on responses to 5-hydroxy-tryptamine." European J.Pharmacology. 231. 259-265 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Liu G.J.and Takeuchi H.: "Modulation of neuropeptide effects by achatin-I,an Achatina endogenous tetrapeptide." European J.Pharmacology. 240. 139-145 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Liu G.J.and Takeuchi H.: "AJ-2615,a long-acting Ca^2 channel antagonist with a novel structural type." European J.Pharmacology. 231. 91-95 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Liu G.J.and Takeuchi H.: "Effects of cyclic AMP and IP_3 intra-cellularly injected into the identifiable Achatina giant neurones." Comparative Biochemistry and Physiology. 104C. 199-204 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Santos D.E.and Takeuchi H.: "Influence of drugs for membrane excitability modification on the excitation caused by achatin-I." Comparative Biochemistry and Physiology. 105C. 185-188 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Liu G.J.,Santos D.E.and Takeuchi H.: "Sensitivities of Achatina giant neurones to peptides isolated from Mollusca." Acta Biologica Hungarica. 44. 25-28 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takeuchi H.,Santos D.E.,Liu G.J.,Araki Y.,Zhang W.,Emaduddin M.and Kakitsuba N.: "Identifications in the ganglia and neurotransmitters of giant neurones of an African giant snail(Achatina fulica Ferussac)." Proceeding of Malacological Society of the Philippines.62-84

    • Related Report
      1993 Annual Research Report
  • [Publications] Takeuchi H.: "Isolation and effects of achatin-I,a neuroexcitatory tetrapeptide from the ganglia of an African giant snail(Achatina fulica Ferussac)" Acta Manilana. (印刷中).

    • Related Report
      1993 Annual Research Report
  • [Publications] 劉国君,ディビナ・E・サントス,ムハンマド・エマドゥディン・荒木陽子,竹内宏: "Achatin-Iの神経修飾作用." 神経化学. 32. 254-255 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] ディビナ・E・サントス,劉国君,張唯,荒木陽子,竹内宏: "Triprolidineのachatin-Iに対する修飾作用." 神経化学. 32. 458-459 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Santos,E,Liu,G.J.,TAKEUCHI,H.,HASHIMOTO,K.,Deura,S.: "Further identification of giant neurones in the pedal ganglia of Achatina fulica Ferussac." Comparative Biochemistry and physiology. 102C. 373-377 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Liu,G.J.,TAKEUCHI,H.: "Modulatory effects of achatin-I, an Achatina endogenous neuroactive peptide,on responses to 5-hydroxytryptamine." European J.Pharmacology.

    • Related Report
      1992 Annual Research Report
  • [Publications] Liu,G.J.,TAKEUCHI,H.: "Effects of cyclic AMP,cyclic GMP and IP_3 intracellularly injected into the identifiable Achatina giant neu.." Comparative Biochemistry and physiology.

    • Related Report
      1992 Annual Research Report
  • [Publications] Santos,D.E.,TAKEUCHI,H.: "Influence of the drugs for membrane excitability modification on the excitation caused by achatin-I." Comparative Biochemistry and Physiology.

    • Related Report
      1992 Annual Research Report
  • [Publications] TAKEUCHI,H.,Kim,K.H.,Liu,G.J.,YASUDAKAMATANI,Y.,Mi: "Achatin-I,an excitatory neurotransmitter having a D-phenylalanine residue of Achatina giant neurones" In″Invertebrate Neurobiology″,Akademiai Kiudo,Budapest,

    • Related Report
      1992 Annual Research Report
  • [Publications] Liu,G.J.,Santos,D.E.,TAKEUCHI,H,.pongchaidecha-Yon: "Sensitivities of Achatina giant neurones to peptides isolated from Mollusca." In″Invertebrate Neurobiology″,Akademiai Kiudo,Budapest,

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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