Signal transduction systems of achatin-I,a neuropeptide having a D-phenylalanine residue.

achatin-I（一种具有 D-苯丙氨酸残基的神经肽）的信号转导系统。

基本信息

批准号：
06680758
负责人：
TAKEUCHI Hiroshi
金额：
$ 0.96万
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：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06680758/
关键词：
Signal transduction Achatin-I Neuropeptide D-Amino acid Voltage clamp Molluscan giant neurone

项目摘要

The effect of intracellular signal transduction system inhibitors on the inward current (I_<in>) caused by achatin-I,an Achatina endogenous tetrapeptide having a D-phenylalanine residue, applied locally onto the neurone tested, were examined under voltage clamp using two identifiable Achatina giant neurone types, v-RCDN and PON.H-89 (PKA inhibitor) markedly suppressed the achatin-I-induced I_<in> on PON, whereas this drug was ineffective on the I_<in> of v-RCDN.Dose (pressure duration)-response study of achatin-I on PON in a physiological solution and in the presence of H-89, and Lineweaver-Burk plot of these data, indicated that H-89 inhibited the I_<in> in noncompetitive manner. KT5823 (PKG inhibitor) suppressed the achatin-I-induced I_<in> of v-RCDN in mainly noncompetitive and partly uncompetitive manners, but this drug had no effect on the I_<in> of PON.W-7 (calmodulin inhibitor) suppressed noncompetitively the I_<in> of PON,but this drug had no effect on the I_<in> of v-RCDN.IBMX (cyclic nucleotide phophodiesterase inhibitor) enhanced the achatin-I-induced I_<in> of v-RCDN,but this drug was ineffective on the I_<in> of PON.However, IBMX might have effects on the achatin-I receptor sites on v-RCDN.These findings suggest multiple intracellular signal transduction pathways mediating the achatin-I-induced I_<in> : the I_<in> of PON is via PKA and probably Ca^<2+>/calmodulin-dependent protein kinase, and the I_<in> of v-RCDN via PKG.Other signal transduction system inhibitors including calphotin C (PKC inhibitor) did not significantly affect the I_<in> of both v-RCDN and PON.

细胞内信号转导系统抑制剂对由 achatin-I（一种具有 D-苯丙氨酸残基的 Achatina 内源性四肽）引起的内向电流 (I_<in>) 的影响，局部施加到测试的神经元上，使用两个可识别的电压钳在电压钳下检查Achatina 巨神经元类型、v-RCDN 和 PON.H-89（PKA 抑制剂）显着抑制 PON 上的 achatin-I 诱导的 I_<in>，而该药物对 v-RCDN 的 I_<in> 无效。在生理溶液中和 H-89 存在的情况下，achatin-I 对 PON 的剂量（压力持续时间）-反应研究，以及这些的 Lineweaver-Burk 图数据表明H-89以非竞争性方式抑制I_<in>。 KT5823（PKG抑制剂）主要以非竞争性和部分非竞争性方式抑制achatin-I诱导的v-RCDN I_<in>，但该药物对PON.W-7（钙调蛋白抑制剂）的I_<in>没有影响非竞争性抑制PON的I_<in>，但该药对v-RCDN.IBMX（环核苷酸）的I_<in>没有影响磷酸二酯酶抑制剂)增强了achatin-I诱导的v-RCDN I_<in>，但该药物对PON的I_<in>无效。然而，IBMX可能对v-RCDN上achatin-I受体位点有影响这些发现表明多种细胞内信号转导途径介导achatin-I诱导的I_<in>：PON的I_<in>是通过PKA并且可能Ca^2+/钙调蛋白依赖性蛋白激酶，以及通过 PKG 的 v-RCDN 的 I_<in>。其他信号转导系统抑制剂，包括钙磷蛋白 C（PKC 抑制剂），对两种 v 的 I_<in> 没有显着影响-RCDN 和 PON。