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

1995 年度 実績報告書

• 研究課題/領域番号: 06680758
• 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 岐阜大学, 医学部, 助教授 (00212316)
• 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,神経作用性ペプチド,achatin-I(Gly-D-Phe-Ala-Asp)により,アフリカマイマイ(Achatinafulica)神経節に同定される2つの巨大神経細胞,PON(periodically oscillating neurone)とv-RCDN(ventral-right cerebral distinct neurone)に引き起こされる内向き電流(I_<in>)細胞内シグナル伝達機構を研究した.昨年度の研究では,achatin-IによりPONに引き起こされるI_<in>は,H-89(protein kinase A(PKA)inhibitor)ならびにW-7(calmodulin inhibitor)により抑制されることを証明した.一方このペプチドによりv-RCDNに引き起こされるI_<in>に対しては,H-89もW-7も作用がなかった.
本年度は,これら2種のAchatina巨大神経細胞でachatin-Iにより引き起こされるI_<in>に対して,KT5823(protein kibase G(PKG)inhibitor),calphostin C (protein kinasem C inhibitor),ML-9(mcosin-light-chain kinase inhibitor),genistein(tyrosin protein kinase inhibitor),fluphenazine nitrogen-mustard(calmodulin-dependent phosphodiesterase inhibitor),indomethacin(prostaglandin cyclooxy-genase inhibitor),okadaic acidおよびcalyculin A(protein phosphatase inhibitor)が作用を示すかどうか検定した.
PONにおけるI_<in>は,本年度検定されたKT5823以下のシグナル伝達機構抑制物質により,まったく影響を受けなかった.これに反してv-RCDNにおけるI_<in>は,KT5823により顕著に抑制された.昨年および本年の研究結果により,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I_<in>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] 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).