Neurophysiological and neuropharmacological investigations of achatin-I, a neuroactive peptide having a D-Phe residue.

achatin-I（一种具有 D-Phe 残基的神经活性肽）的神经生理学和神经药理学研究。

• 批准号: 02670049
• 负责人: TAKEUCHI Hiroshi
• 金额: $ 1.41万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670049/
• 关键词: Peptides; D-Amino acids; Neuroactive; Neurotransmitter; Neuromodulator; Giant neurones; African giant snail; Mollusca; ペプチド; 膜電位固定法; Dー型アミノ酸

A neuroexcitatory tetrapeptide having a D-phenylalanine residue (Gly-D-Phe-L-Ala-L-Asp), termed achatin-I, has been isolated from the ganglia of an African giant snail (Achatina fulica Ferussac). We demonstrated that achatin-I is acting as an excitatory neurotransmitter and a neuromodulator to Achatina giant neurones, supported partly by this fund in 1990-92.1. Of the eight possible stereoisomers of achatin-I, only achatin-I showed marked excitatory effects on these giant neurones. Among twenty-three Achatina neurone types tested, the ten types were excited by achatin-I. With these findings, we proposed that achatin-I is acting as an excitatory neurotransmitter of these neurones. The effects of the peptide was due to the membrane permeability increase to Na^+ (in 1990).2. The structure-activity relationships of achatin-I and its derivatives were studied. Among these compounds, only achatin-I had marked effects, indicating that the effects were not only stereo-specific but also structur … More e-specific on these neurones (in 1991).3. We looked for the drugs antagonistic to the achatin-I excitation by testing the known blockers of the small molecule neurotransmitters. We found that the three histamine (H_1) blockers, triprolidine, homochlorcyclidine and trimeprazine, antagonized the achatin-I excitation. These effects were not due to the effects of histamine (H_1) antagonists, since the majority of H_1 blockers tested were not effective on the achatin-I excitation. The known blockers of other small molecule neurotransmitters including H_2 blockers showed no effect on the achatin-I excitation.A component of the excitation caused by 5-hydroxytryptamine (5-HT) was facilitated by achatin-I at 3 x 10^<-6> M, which was lower than its ED_<50> for the direct excitation. Of the neuroactive peptides originally isolated from Mollusca, the effects of oxytocin and APGW-amide were suppressed by achatin-I, whereas those of FMRFamide were facilitated. Based on these results, it is considered that achatin-I is acting to the Achatina neurones also as a neuromodulator (in 1992). Less

从非洲大蜗牛（AchatinafulicaFerussac）的神经节中分离出一种具有D-苯丙氨酸残基的神经兴奋性四肽（Gly-D-Phe-L-Ala-L-Asp），命名为achatin-I。我们证明achatin-I是作为一种兴奋性神经递质和神经调质的Achatina巨大的神经元，部分支持该基金在1990- 92。1。八个可能的立体异构体的achatin-I，只有achatin-I表现出显着的兴奋作用，这些巨大的神经元。在所测试的23种Achatina神经元类型中，有10种类型被achatin-I兴奋。根据这些发现，我们提出achatin-I是作为这些神经元的兴奋性神经递质。该肽的作用是由于膜对Na^+的渗透性增加（1990年）.研究了achatin-I及其衍生物的构效关系。在这些化合物中，只有achatin-I具有显着的作用，表明其作用不仅具有立体特异性，而且具有结构特异性 ...更多信息 在这些神经元上的e特异性（在1991年）。我们通过测试已知的小分子神经递质阻断剂来寻找对抗achatin-I兴奋的药物。我们发现三种组胺（H_1）阻断剂曲普利啶、高氯环啶和曲美拉嗪都能拮抗Achatin-I的兴奋作用。这些作用不是由于组胺（H_1）拮抗剂的作用，因为大多数H_1阻断剂对achatin-I兴奋无效。其他小分子神经递质的阻断剂（包括H_2阻断剂）对Achatin-I的兴奋无影响，Achatin-I在3 × 10 ~ 4 μ M时易化5-羟色胺（5-HT）引起的兴奋<-6>成分，但低于其直接兴奋的艾德_（ED）<50>。最初从软体动物中分离的神经活性肽，催产素和APGW-酰胺的影响被抑制achatin-I，而FMRFamide的促进。基于这些结果，认为achatin-I也作为神经调质作用于Achatina神经元（1992年）。少

项目成果

Liu, G. J. and Takeuchi, H.: "Modulatory effects of achatin-I, an Achatina endogenous neuroactive peptide, on responses to 5-hydroxytryptamine." European J. Pharmacol.

Liu, G. J. 和 Takeuchi, H.：“achatin-I（一种 Achatina 内源性神经活性肽）对 5-羟色胺反应的调节作用。”

Liu,G.J.,Santos,D.E.,Takauchi,H.,Pongchaidecha-Yongsiri,A.: "Sensitivities of Achatina giant neurones to peptides isolated from Mollusca." In “Invertebrate Neurobiology",Akademiai Kiudo,Budapest,

Liu, G.J.、Santos, D.E.、Takauchi, H.、Pongchaidecha-Yongsiri, A.：“Achatina 巨型神经元对从软体动物中分离出的肽的敏感性”，《无脊椎动物神经生物学》，Akademiai Kiudo，布达佩斯，

Kamatani,Y.,Minakata,H.,Nomoto,K.,Kim,K.H.,Yongsiri,A.& Takeuchi,H.: "Isolation of achatinーI,a neuroactive tetrapeptide having a Dーphenylalanine residee,from Achatina ganglia,and its effects on Achatina giant neurones." Comp.Biochem.Physiol.98C. 97-103 (1

Kamatani, Y.、Minakata, H.、Nomoto, K.、Kim, K.H.、Yongsiri, A. 和 Takeuchi, H.：“从 Achatina 神经节中分离出 achatin-I，一种具有 D-苯丙氨酸驻留的神经活性四肽，及其对 Achatina 巨神经元的影响。”Comp.Biochem.Physiol.98C.97-103 (1

Takeuchi,H.,Kim,K.H.,Liu,G.J.,Yasuda-Kamatani,Y.et al.: "Achatin-I,an excitatory neurotransmitter having a D-phenylalanine residue of Achatina giant neurones." In "Invertebrate Neurobiology",Akademiai Kiudo,Budapest,

Takeuchi,H.,Kim,K.H.,Liu,G.J.,Yasuda-Kamatani,Y.等人：“Achatin-I，一种兴奋性神经递质，具有 Achatina 巨神经元的 D-苯丙氨酸残基。”

Kim, K. H., Takeuchi, H., Kamatani, Y., Minakata, H. and Nomoto, K.: "Slow inward current induced by achatin-I, an endogenous tetrapeptide having a D-phenylalanine residue, of Achatina neurones." European J. Pharmacol.194. 99-106 (1991)

Kim, K. H.、Takeuchi, H.、Kamatani, Y.、Minakata, H. 和 Nomoto, K.：“由 Achatin-I（一种具有 D-苯丙氨酸残基的内源性四肽）诱导的 Achatina 神经元的缓慢内向电流。”