D-phenylalanineを持つ神経ペプチドachatin-Iの情報伝達機構

• 研究課題/領域番号: 06680758
• 研究種目: 一般研究(C)
• 配分区分: 補助金
• 研究分野: 神経化学・神経薬理学
• 研究機関: 岐阜大学
• 研究代表者: 竹内 宏 岐阜大学, 医学部, 教授 (10033333)
• 研究分担者: 外崎 肇一 岐阜大学, 農学部, 教授 (30103485) ; 山本 典子 岐阜大学, 医療技術短期大学部, 教授 (70021409) ; 荒木 陽子 岐阜大学, 医学部, 助手 (20176374) ; 李 憲 (季 憲) 岐阜大学, 医学部, 助教授 (00212316)
• 研究期間 (年度): 1994 – 1995
• 研究課題ステータス: 完了 (1995年度)
• 配分額: 1,500千円 (直接経費: 1,500千円); 1995年度: 400千円 (直接経費: 400千円); 1994年度: 1,100千円 (直接経費: 1,100千円)
• キーワード: 細胞内情報伝達機構 / アカチン-I / 神経作用性ペプチド / D-型アミノ酸 / 膜電位固定 / 軟体動物巨大神経細胞

研究概要

本研究では2年間にわたり,アフリカマイマイ(Achatina fulica Ferussac)神経節中に同定される2種の巨大神経細胞,PON(periodically oscillating neurone)とv-RCDN(ventral-right cerebral distinct neurone)を用いて,D-phenylalanine残基を持った内在性神経ペプチド,achatin-I(Gly-D-Phe-Ala-Asp)により引き起こされる内向き電流(Iin)の細胞内シグナル伝達機構を研究した.すなわちこれら2種の神経細胞におけるIinに対する,H-89(protein kinase A (PKA) inhibitor),KT5823(protein kinase G (PKG) inhibitor),calphostin C(protein kinase C inhibitor), IBMX (cyclic AMP phosphodiesterase inhibitor), W-7 (calmodulin inhibitor), ML-9(myosin light-chain kinase inhibitor), genistein (tyrosine protein kinase inhibitor), fluphenazine nitrogen-mustard (calmodulin-dependent phosphodiesterase inhibitor),indomethacin (prostaglandin cyclooxygenase inhibitor), okadaic acid および calyculin A (protein phosphatase inhibitor)の作用を検定した.
PONでachatin-Iにより引き起こされたIinは,H-89ならびにW-7により顕著に抑制され,IBMXにより軽度に増強された.これに反してv-RCDNにおけるIinは,これらの薬物によりまったく影響されなかった.一方v-RCDNのIinは,KT5823により著しく抑制されたが,PONのIinはまったく影響されなかった.これらの結果より,神経作用性ペプチドachatin-Iは,2種の巨大神経細胞PONとv-RCDNに同様なNa^+依存性のIinを引き起こすが,そのシグナル変換機構はおそらく異なっており,PONではPKAとCa^<2+>/calmodulin-dependent protein kinaseにより,v-RCDNではPKGによると考えられる.

研究成果

• [文献書誌] Liu Guo Jun: "Suppressing effects of neuroactive peptides on the inward current caused by achatin-I, an Achatina endogenous peptide." General Pharmacology. 26. 765-772 (1994)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Takeuchi Hiroshi: "Pharmacological characteristics of Monatepil maleate (AJ-2615), a novel structure Ca2+-entry blocker, with antihypertensive, antiatherosclerotic. α 1-adrenocaptor antagonistic. and antidyslipidemic effects." Cardiovasc. Drug. Rev.12. 254-269 (1994)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Santos Divina E.: "Blockers for excitatory effects of achatin-I, a tetrapeptide having a D-phenylalanine residue, on a snail neurone." European J. Pharmacology. 272. 231-239 (1995)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Emaduddin Muhammad: "Effects of dopamine on snail neurone." European J. Pharmacology. 238. 113-124 (1995)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Araki Yoko: "Further mapping of the Achatina giant neurone types sensitive to the neuroactive peptides isolated from invertebrates." General Pharmacology. 26. 1701-1708 (1995)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Takeuchi Hiroshi: "Further study on the effects of achatin-I, an Achatina endogenous neuroexcitatory tetrapeptide having a D-phenylalanine residue, on Achatina neurones." Acta Biol. Hungarica. 46. 395-400 (1995)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Han Xiao Yan: "Modulation by APGW-amide, an Achatina endogenous inhibitory tetrapeptide, on currents induced by neuroactive compounds on Achatina neurones. I. Amines and amino acids." General Pharmacology. (in press).
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Han Xiao Yan: "Modulation by APGW-amide, an Achatina endogenous inhibitory tetrapeptide, on currents induced by neuroactive compounds on Achatina neurones. II. Peptides." General Pharmacology. (in press).
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Zhang Wei: "Pharmacological characteristics of excitatory GABA receptors in a snail neurones." General Pharmacology. (in press).
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Emaduddin Muhammad: "Lineweaver-Burk analysis for the blocking effects of mammalian dopamine receptor antagonists on dopamine-induced currents in Achatina giant neurones." Gerenal Pharmacology. (in press).
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Emaduddin Muhammad: "Effects of achatin-I (Gly-D-Phe-L-Ala-L-Asp) analogues having a dehydrophenylalanine or aminoisobutyric acid residue, on Achatina giant neurones."
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Emaduddin Muhammad: "Multiple intracellular signal transduction pathways mediating inward current produced by the neuropeptide, achatin-I." European J. Pharmacology. (in press).
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Salunga Thucydides L.: "Blocking effects of promethazine, triprolidine and their analogues on the excitation caused by the neuropeptide, achatin-I." European J. Pharmacology. (in press).
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Takeuchi Hiroshi: "Identifiable Achatina giant neurones: their localizations in ganglia, axonal pathways and pharmacological reatures." General Pharmacology. (in press).
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Zhang Wei: "Effects of L-glutamic acid and its agonists on snail neurones." General Pharmacology. (in press).
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Zhang Wei: "Pharmacological characteristics of an outward current produced by β-hydroxy-L-glutamic acid on a snail neurone." General Pharmacology. (in press).
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Zhang Wei: "Ouabain-sensitive K'-dependent outward current caused by threo-β-hydroxy-L-glutamic acid on a snail neurone." General Pharmacology. (in press).
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Takeuchi Hiroshi: "Neuroexcitatory tetrapeptide having a D-phenylalanine residue, achatin-I, isolated from the ganglia of an African giant snail (Achatina fulica Ferussac)." "Environment and Physiology", ed. by Mallick B. N. and Singh S., Narosa Publishing House, New Delhi, India., 41-53 (1994)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Liu G.J.and Takeuchi H.: "Suppressing effects of neuroactive peptides on the inward current caused by achatin-I,an Achatina endogenous peptide." Gen.Pharmacol.26. 765-772 (1994)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Takeuchi H., Liu G.J., Hosoki K.and Karasawa T.: "Pharmacological characteristics of Monatepil maleate (AJ-2615), a novel structure Ca2+-entry blocker, with antihypertensive, antiatherosclerotic, alpha1-adrenocaptor antagonistic, and antidyslipidemic effects." Cardiovasc.Drug.Rev.12. 254-269 (1994)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Sanots 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." Fur.J.Pharmacol.272. 231-239 (1995)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Emaduddin M., Liu G.J.and Takeuchi H.: "Effects of dopamine on snail neurone" Eur.J.Pharmacol.238. 113-124 (1995)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Takeuchi H., Liu G.J., Kim K.H., Santos D.E., Emaduddin M., Zhang W.and Araki Y.: "Neuroexcitatory tetrapeptide having a D-phenylalanine residue, achatin-I,isolated from the ganglia of an African giant snail (Achatina fulica Ferussac)." "Environment and Physiology", ed.by Mallick B.N.and Singh S., Narosa Publishing house, New Delhi, India.41-53 (1994)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] 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.26. 1701-1708 (1995)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Takeuchi H., Emaduddin M., Araki Y., Zhang W., Han S.Y., Salunga T.L.and Wong S.M.: "Further study on the effects of achatin-I,an Achatina endogenous neuroexcitatory tetrapeptide having a D-phenylalanine residue, on Achatina neurones." Acta Biol.Hun.46. 395-400 (1995)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Emududdin M., Liu G.J., and Takeuchi H.: "Multiple intracellular signal transduction pathways mediating inward current produced by the neuropeptide, achatin-I." Euro.J.Pharmacol.(in press).
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Salunga T.L., Han X.Y., Wong S.M., Takeuchi H., Upton C.and Mercer A.D.: "Blocking effects of promethazine, triprolidine and their analogues on the excitation caused by the neuropeptide, achatin-I." Eur.J.Pharmacol.(in press).
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Takeuchi H., Araki Y., Emaduddin M., Zhang W., Han X.Y., Salunga T.L.and Wong S.M.: "Identifiable Achatina giant neurones : their localizations in ganglia, axonal pathways and pharmacological features." Gen.Pharmacol.(in press).
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Zhang W., Liu G.J., Takeuchi H.and Kurono M.: "Effects of L-glutamic acid and its agonists on snail neurones." Gen.Pharmacol.(in press).
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Zhang W., Takeuchi H.and Kurono M.: "Pharmacological characteristics of an outward current produced by beta-hydroxy-L-glutamic acid on a snail neurone." Gen.Pharmacol.(in press).
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Zhang W., Emaduddin M., Takeuchi H.and Kurono M.: "Ouabain-sensitive K+-dependent outward current caused by threo-beta-hydroxy-L-glutamic acid on a snail neurone." Gen.Pharmacol.(in press).
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Han X.Y., Salunga T.L., Zhang W.and Takeuchi H.: "Modulation by APGW-amide, an Achatina endogenous inhibitory tetrapeptide, on currents induced by neuroactive compounds on Achatina neurones. I.Amines and amino acids." Gen.Pharmacol.(in press).
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Han X.Y., Salunga T.L., Zhang W.and Takeuchi H.: "Modulation by APGW-amide, an Achatina endogenous inhibitory tetrapeptide, on currents induced by neuroactive compounds on Achatina neurones. II.Peptides." Gen.Pharmacol.(in press).
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Zhang W., Han X.Y.and Takeuchi H.: "Pharmacological characteristics of excitatory GABA receptors in a snail neurones" Gen.Pharmacol.(in press).
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Emaduddin M.and Takeuchi H.: "Lineweaver-Burk analysis for the blocking effects of mammalian dopamine receptor antagonists on dopamine-induced currents in achatina giant neurones." Gen.Pharmacol.(in press).
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Emaduddin M., Takeuchi H., Jain R.M.and Chauhan V.S.: "Effects of achatin-I (Gly-D-Phe-L-Ala-L-Asp) analogues having a dehydrophenylalanine or aminoisobutyric acid residue, on Achatina giant neurones." Gen.Pharmacol.(in press).
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Santos Divina E.: "Blockers for excitatory effects of achatin-I. a tetrapeptide having a D-phenylalanine residue. on a snail neurone." European J. Pharmacology. 272. 231-239 (1995)
• [文献書誌] Emaduddin Muhammad: "Effects of dopamine on snail neurone." European J. Pharmacology. 238. 113-124 (1995)
• [文献書誌] Araki Yoko: "Further mapping of the Achatina giant neurone types sessitive to the neuroactive peptides isolated from invertebrates." General Pharmacology. 26. 1701-1708 (1995)
• [文献書誌] Takeuchi Hiroshi: "Further study on the effects of achatin-I. an Achatina endogenous neuroexcitatory tetrapeptide having a D-phenylalanine residue. on Achatina neurones." Acta Biol. Hungarica. 46. 395-400 (1995)
• [文献書誌] Emaduddin Muhammad: "Multiple intracellular signal transduction pathways mediating inward current produced by the neuropeptide. achatin-I." European J. Pharmacology. (in press).
• [文献書誌] Salunga Thucydides L.: "Blocking effects of promethazine. triprolidine and their analogues on the excitation caused by the neuropeptide. achatin-I." European J. Pharmacology. (in press).
• [文献書誌] Takeuchi Hiroshi: "Identifiable Achatina giant neurones: their localizations in ganglia. axonal pathaways and pharmacological features." General Pharmacology. (in press).
• [文献書誌] Zhang Wei: "Effects of L-glutamic acid and its agonists on snail neurones." General Pharmacology. (in press).
• [文献書誌] Zhang Wei: "Pharmacological characteristics of an outward current produced by β-hydroxy-L-glutamic acid on a snail neurone." General Pharmacology. (in press).
• [文献書誌] Zhang Wei: "Ouabain-sensitive K'-dependent outward current caused by threo-β-hydroxy-L-glutamic acid on a snail neurone." General Pharmacology. (in press).
• [文献書誌] Han Xiao Yan: "Modulation by APGW-amide. an Achatina codogenous inhibitory tetrapeptide. on currents induced by neuroactive compounds on Achatina neurones. I. Amines and amino acids." General Pharmacology. (in press).
• [文献書誌] Han Xiao Yan: "Modulation by APGW-amide. an Achatina codogenous inhibitory tetrapeptide. on currents induced by neuroactive compounds on Achatina neurones. II. Peptides." General Pharmacology. (in press).
• [文献書誌] Zhang Wei: "Pharmacological characteristics of excitatory GABA receptors in a snail neurones." General Pharmacology. (in press).
• [文献書誌] Emaduddin Muhammad: "Lincweaver-Burk analysis for the blocking effects of mammalian dopamine receptor antagonists on dopamine-induced currents in Achatina giant neurones." Gerenal Pharmacology. (in press).
• [文献書誌] Emaduddin Muhammad: "Effects of achatin-I(Gly-D-Phe-L-Ala-Asp)analogues having a dehydrophenylalanine aminoisobutyric acid residue. on Achatina giant neurones." Gerenal Pharmacology. (in press).
• [文献書誌] 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)
• [文献書誌] Takeuchi H.,Liu G.J.,Hosoki K.and Karasawa T.: "Pharmacolosicnl characteristics of Monatopii malento(AJ-2615).a novel structure Ca^<2+>-ontry blocker.with antihyportensivo.antintheroscierotic.α 2-adrenocoptor antagonistic.and antidysiipidemic effects." Cardiovasc.Drug Rev.in press.
• [文献書誌] 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.
• [文献書誌] 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.
• [文献書誌] Takeuchi H.: "Isolation and effects of achatin-I,a neuroexcitatory tetrapeptide from the ganglia of an african giant snail(Achatina fulica Ferussac)." Acta Manilana. 41. 41-59 (1993)
• [文献書誌] 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)
• [文献書誌] 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, (1993)
• [文献書誌] Takeuchi H.,Liu G.J.,Kim K.H.,Santos D.E.,Enaduddin M.,Zhang W.and Araki Y.: "Environment and Physiology" Mallick B.N.and Singh S.,Narosa Publishing House, (1994)