Isolation and characterization of a receptor candidate for L-DOPA in C.elegans

线虫中 L-DOPA 候选受体的分离和表征

• 批准号: 14380360
• 负责人: GOSHIMA Yoshio
• 金额: $ 10.88万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14380360/
• 关键词: L-DOPA; transmitter; receptor; G-protein; C.elegns; pumping behavior; chemosensory; Xenopus; L-ドーパ; 神経伝達物質; GPCR; 知覚神経; G蛋白連関型受容体; アミノ酸; 生理活性物質; パーキンソン病; ドパミン

We have identified a candidate receptor for L-DOPA (CeDOPAR) in C.elegans. CeDOPAR share homology with G protein-coupled receptor. In CeDOPAR-expressed Xenopus laevis oocyte, both L-DOPA (pM order) and L-theo-DOPS (mM order) induced inward current. DOPS-induced response was inhibited by DOPA-CHE, an antagonist for L-DOPA, The immunohistochemistry with specific antibody raised against CeDOPAR, suggests that CeDOPAR expression was regulated at different stages. In adult, CeDOPAR was localized near M1 that is thought to control pharyngeal pumping of the worm. On the dopa-containing agar plate, pumping rate of worm was significantly increased when compared that on control agar plate. RNAi for CeDOPAR suppressed the pumping response to DOPA, thereby indicating that CeDOPAR was a candidate receptor mediating the DOPA-induced behavior in nematode. We are now searching various ligands for CeDOPAR.

我们已经确定了一个候选受体左旋多巴（CeDOPAR）在秀丽隐杆线虫。CeDOPAR与G蛋白偶联受体具有同源性。在表达CeDOPAR的非洲爪蟾卵母细胞中，L-DOPA（pM量级）和L-theo-DOPS（mM量级）均诱导内向电流。L-DOPA拮抗剂DOPA-CHE可抑制DOPS诱导的反应。CeDOPAR特异性抗体的免疫组化结果表明，CeDOPAR的表达在不同时期受到调节。在成虫中，CeDOPAR位于M1附近，被认为控制蠕虫的咽部泵送。在含有多巴的琼脂平板上，蠕虫的泵血率比在对照琼脂平板上显著增加。针对CeDOPAR的RNAi抑制了对DOPA的泵送反应，从而表明CeDOPAR是介导线虫中DOPA诱导的行为的候选受体。我们现在正在寻找CeDOPAR的各种配体。

项目成果

Yamanashi K: "Involvement of nitric oxide production via kynurenic acid-sensitive glutamate receptors in DOPA-induced depressor responses in the nucleus tractus solitarii of anesthetized rats"Neurosci Res.. 43(3). 231-238 (2002)

Yamanashi K：“通过犬尿酸敏感谷氨酸受体产生一氧化氮参与麻醉大鼠孤束核中多巴诱导的抑制反应”Neurosci Res.. 43(3)。

Misu Y: "Is DOPA a neurotransmitter?"Trends Pharmacol.Sci.. 23. 262-268 (2002)

Misu Y：“多巴是一种神经递质吗？”Trends Pharmacol.Sci.. 23. 262-268 (2002)

Ibi M: "Isolation and characterization of a receptor candidate For L-DOPA in C.elegans"Neurosci Res.Suppl.. 26. S101 (2002)

Ibi M：“线虫中 L-DOPA 候选受体的分离和表征”Neurosci Res.Suppl.. 26. S101 (2002)

Misu Y: "DOPA causes glutamate release and delayed neuron death by brain ischemia in rats"Neurotoxicol Teratol.. 24(5). 629-638 (2002)

Misu Y：“多巴导致大鼠脑缺血导致谷氨酸释放和延迟神经元死亡”Neurotoothol Teratol.. 24(5)。

Misu Y: "Is DOPA a neurotransmitter?"Trends Pharmacol Sci.. 23(6). 262-268 (2002)

Misu Y：“多巴是一种神经递质吗？”Trends Pharmacol Sci.. 23(6)。