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

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具有显著的作用，表明这种作用不仅是立体专一的，而且是结构专一的 ...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

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