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

具有D-苯基丙氨酸住所（Gly-D-Phe-L-Ala-L-Asp）的神经兴奋性远肽已被称为achatin-I，已从非洲巨型蜗牛的神经节中分离出来。我们证明了Achatin-I充当兴奋性神经递质和对Achatina巨型神经元的神经调节剂，在1990 - 92.1的一部分得到了该基金的支持。在achatin-I的八个可能的立体异构体中，只有achatin-i对这些巨型神经元显示出明显的兴奋作用。在测试的二十三种Achatina神经元类型中，十种类型被Achatin-I激发。通过这些发现，我们提出Achatin-I充当这些神经元的令人兴奋的神经递质。胡椒的作用是由于膜的通透性增加到Na^+（1990年）。2。 Achatin-I及其衍生物的结构活性关系是研究的。在这些化合物中，只有achatin-i具有明显的作用，表明该作用不仅是立体声特异性的，而且是结构性的……在这些神经元上更特异性（1991年）。3。我们通过测试小分子神经递质的已知阻滞剂来寻找对achatin-I的拮抗剂。我们发现，三个组胺（H_1）阻滞剂，三洛莱丁，同氯环肽和三氯丙嗪使Athatin-I感到兴奋。这些影响并不是由于组胺（H_1）拮抗剂的作用，因为大多数测试的H_1阻滞剂对Achatin-I兴奋无效。包括H_2阻滞剂在内的其他小分子神经递质的已知阻滞剂对Achatin-I兴奋没有影响。由Achatin-i在3 x 10^<-6> M时制备了由5-羟色胺（5-HT）引起的兴奋的组成部分，该兴奋性是在3 x 10^<-6> M中，其较低的ED_ <50>对于eD_ <50>而言。在最初从Mollusca分离的神经活性宠物中，催产素和APGW-酰胺的作用被achatin-I抑制，而制备了FMRFAMIDE的作用。基于这些结果，achatin-I也作为神经调节剂对Achatina神经元作用（1992年）。较少的

项目成果

Liu,G.J.,Santos,E.Takeuchi,H.et al.: "APGW-amide as an inhibitory neurotransmitter of Achatina fulica Ferussac." Biochem.Biophys.Research Communications. 177. 27-33 (1991)

Liu,G.J.,Santos,E.Takeuchi,H.et al.：“APGW-酰胺作为 Achatina fulica Ferussac 的抑制性神经递质。”

Kim, K. H., Takeuchi, H., Kamatani, Y., Minakata, H. and Nomoto, K.: "tructure-activity relationship studies on the endogenous neuro-ative tetrapeptide achatin-I on giant neurones of Achatina fulica Ferussac." Life Sci., Pharmacol. Lett.48. 91-96 (1991)

Kim, K. H.、Takeuchi, H.、Kamatani, Y.、Minakata, H. 和 Nomoto, K.：“内源性神经活性四肽 achatin-I 对 Achatina fulica Ferussac 巨神经元的结构-活性关系研究”。

Kim,K.H.,Takeuchi,H.,Kamatani,Y.,Minakata,H.& Nomoto,K.: "Structureーactivity relationship studies on the endogenous neuroactive tetrapeptide achatinーI on giant neurons of Achatina fulica Fe^^´russac." Life Sciences,Pharmacology Letters.48. 91-96 (1991)

Kim, K.H.、Takeuchi, H.、Kamatani, Y.、Minakata, H. 和 Nomoto, K.：“对 Achatina fulica Fe^^´russac 巨型神经元内源性神经活性四肽 achatin-I 的结构-活性关系研究。 “生命科学，药理学快报。48。91-96（1991）

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

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，