Functional analysis of novel G-coupled receptor candidate for L-DOPA and structural determination of its ligands

L-DOPA新型G偶联受体候选物的功能分析及其配体的结构测定

• 批准号: 16390068
• 负责人: GOSHIMA Yoshio
• 金额: $ 8.64万
• 依托单位: Yokohama City University Graduate School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390068/
• 关键词: DOPA; Benzaldehyde; Caenorhabditis elegans; chemotaxis; blood pressure control; monoamine receptors; 神経伝達物質; Gタンパク質連関型受容体; NMR; DOPA; DOPS; 3,4-dihydroxybenzaldehyde; 3,4-dihydroxybenzoic acid; C06H5.7; caenorhabditis elegans; xenopus laevi

We proposed L-3,4-dihydroxyphenylalanine (DOPA) as a neurotransmitter candidate of baroreceptor afferent neurons terminating in the nucleus tractus solitarii (NTS). We have isolated C.elegans C06H5.7 gene as a receptor candidate for DOPA through expression screening using Xenopus laevisoocytes. Electrophysiological analyses of C06H5.7 showed that C06H5.7 responded to non-amine metabolites of DOPA, but did not to itself. Previously, we have reported that 3,4-dihydroxybenzaldehyde (DHBALD) acts as one of active ligands for C06H5.7. An odorant benzaldehyde that is similar to DHBALD in the chemical structure electrophysiologically activated C06H5.7. Although benzaldehyde at low concentrations sensed by AWC sensory neurons is a chemoattractants in C.eleagans, expression of C06H5.7 have not yet been detected in AWC. A null mutant candidate for C06H5.7, nj66,was not defective in the attraction by benzaldehyde. On the other hand, benzaldehyde at high concentrations sensed by ASH sensory neurons is a chemorepellent in C.eleagans, but its receptor has not yet been identified. To test the possibility that C06H5.7 is involved in the aversive mechanisms, we are performing the aversion assay of nj66 and detecting the expression of C06H5.7 in the ASH. However, these ligands produced no effects on blood pressure and hear rates of anesthetized rats, when these were microinjected into the nucleus tractus solitarii.

我们提出L-3,4-二羟基苯丙氨酸（DOPA）作为终止于孤束核（NTS）的压力感受器传入神经元的候选神经递质。我们通过非洲爪蟾细胞的表达筛选，分离出秀丽隐杆线虫C06H5.7基因作为多巴受体候选者。 C06H5.7 的电生理分析表明，C06H5.7 对多巴的非胺代谢物有反应，但对其本身没有反应。此前，我们曾报道过3,4-二羟基苯甲醛（DHBALD）是C06H5.7的活性配体之一。一种有气味的苯甲醛，其化学结构与 DHBALD 相似，电生理激活的 C06H5.7。尽管AWC感觉神经元感知的低浓度苯甲醛是秀丽隐杆线虫中的化学引诱剂，但在AWC中尚未检测到C06H5.7的表达。 C06H5.7 的无效突变候选者 nj66 在苯甲醛的吸引方面没有缺陷。另一方面，ASH感觉神经元感知的高浓度苯甲醛是秀丽隐杆线虫的化学驱避剂，但其受体尚未确定。为了测试C06H5.7参与厌恶机制的可能性，我们正在进行nj66的厌恶实验并检测ASH中C06H5.7的表达。然而，当这些配体被显微注射到孤束核中时，这些配体对麻醉大鼠的血压和心率没有产生影响。

项目成果

Neurobiology of DOPA as a neurotransmitter

多巴作为神经递质的神经生物学

• 发表时间: 2005
• 作者: Misu Y;Goshima Y
• 通讯作者: Goshima Y

Semaphorin 3A signaling is mediate via sequential Cdk5 and GSK3beta phosphorylation of CRMP2 : implication of common phosphorylation mechanism underlying axon guidance and Alzheimer's disease

Semaphorin 3A 信号传导通过 CRMP2 的连续 Cdk5 和 GSK3beta 磷酸化介导：轴突引导和阿尔茨海默病潜在的常见磷酸化机制的含义

• 发表时间: 2005
• 期刊: Genes to Cell 10 2
• 作者: Tanigawa;H.;Shimamura M et al.;Uchida Y;内田穣;Shibakawa YS;Arimura N;Shimamura M;Uchida Y et al.
• 通讯作者: Uchida Y et al.

1-3,4-Dihydroxyphenylalanine-inducedc-Fosexpressioniin the CNS under inhibition of central aromatic 1-amino acid decarboxylase.

在中央芳香族 1-氨基酸脱羧酶的抑制下，1-3,4-二羟基苯丙氨酸诱导 CNS 中的 c-Fos 表达。

• 发表时间: 2005
• 期刊: Neuropharmacology (In press)
• 作者: Uchida Y;Goshima Y;Shibakawa M et al.;Arimura N et al.;Uchida Y;内田穣;Arimura N;Shimamura M
• 通讯作者: Shimamura M

Molecular mechanism of axon guidance mediated by phosphorylation of CRMP2

CRMP2磷酸化介导轴突导向的分子机制

• 发表时间: 2005
• 期刊: Seikagaku 77 11
• 作者: Uchida Y;Goshima Y
• 通讯作者: Goshima Y

CRMP2のリン酸化を介した軸索ガイダンスの分子機構

CRMP2磷酸化引导轴突的分子机制

• 发表时间: 2005
• 期刊: 生化学 77・11
• 作者: Morita A;Yamashita N;Sasaki Y;Uchida Y;Nakajima O;Nakamura F;Yagi T;Taniguchi M;Usui H;Katoh-Semba R;Takei K;Goshima Y;Reo Maeda;Uchida Y;中山実;内田穣
• 通讯作者: 内田穣