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）的压力感受性传入神经元的候选神经递质。本研究利用非洲爪蟾卵母细胞进行表达筛选，分离到了作为多巴受体候选基因的秀丽隐杆线虫C06H5.7基因。对C06H5.7的电生理分析表明，C06H5.7对多巴的非胺代谢产物有反应，但对自身无反应。以前，我们已经报道了3，4-二羟基苯甲醛（DHBALD）作为C06H5.7的活性配体之一。一种有气味的苯甲醛，在化学结构上与DHBALD相似，具有电生理活性。尽管AWC感觉神经元感觉到的低浓度苯甲醛是秀丽隐杆线虫中的化学引诱物，但尚未在AWC中检测到C06H5.7的表达。C06H5.7的无效突变体候选者nj 66在被苯甲醛吸引方面没有缺陷。另一方面，ASH感觉神经元感受到的高浓度苯甲醛在秀丽隐杆线虫中是化学排斥剂，但其受体尚未鉴定。为了测试C06H5.7参与厌恶机制的可能性，我们正在进行nj 66的厌恶测定并检测C06H5.7在ASH中的表达。然而，当将这些配体微量注射到孤束核时，这些配体对麻醉大鼠的血压和心率没有影响。

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

Contribution of the medial amygdaloid nucleus to the development of hypertension in spontaneously hypertensive rats

• DOI: 10.1016/j.neulet.2004.04.066
• 发表时间: 2004-07-22
• 期刊: NEUROSCIENCE LETTERS
• 影响因子: 2.5
• 作者: Fukumori, R;Nishigori, Y;Kubo, T
• 通讯作者: Kubo, T

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.

Phosphorylation of Rho kinase regulates CRMP-2 activity in growth cones.

Rho 激酶的磷酸化调节生长锥中的 CRMP-2 活性。

• 发表时间: 2005
• 期刊: Mol Cell Biol 25・22
• 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;影沢達夫;Shibakawa YS;松野健治;Arimura N
• 通讯作者: Arimura N

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