机制-猫眼课题宝

机制

批准号：

6103958

负责人：

TIM G HALES

金额：

$11.93万

依托单位：

UNIVERSITY OF CALIFORNIA LOS ANGELES

依托单位国家：

美国

项目类别：

财政年份：

1998

资助国家：

美国

项目状态：

已结题

起止时间：

1998-09-01 至 1999-07-31

来源：

https://reporter.nih.gov/project-details/6103958

关键词：

G protein calcium channel cell line dopamine endogenous opioid immunocytochemistry in situ hybridization ligands microdialysis opioid receptor prolactin protein sequence protein structure function receptor binding receptor coupling receptor expression

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中文摘要

翻译

阿片样物质和ORL-1受体与Ca ~（2+）偶联的机制及意义通道亚型 1.阿片类药物和阿片肽敏感的分子特性是什么？ Ca 2+通道亚型？ a. ORL- 1受体是否像阿片受体一样与L型钙通道偶联当在GH 3细胞中表达时， B.不同的L型钙通道α 1亚基转录本是由GH 3细胞表达的 C. A1亚基的反义寡核苷酸是否能消除阿片样物质，钙离子敏感的钙电流成分？ D. HEK 293细胞表达的阿片受体和ORL-1受体与Ca ~（2+）偶联吗通道形成的a10亚基？ 2.什么样的G蛋白机制将阿片和ORL-1受体与CA 2+偶联渠道？ a.是否有一个共同序列，在这个序列上BG与所有阿片类药物结合，钙调素FQ调节钙通道？ B.模拟这种序列的肽是否阻止受体与L- GH 3细胞的Ca 2+通道？ C.类似的方法能将阿片受体从a1 a，a1 b和a1 d上分离出来吗 HEK 293细胞中的Ca 2+通道 3. L型钙通道相对于其他钙通道的贡献是什么？效应子，在阿片类药物和阿片肽调节囊泡释放中的作用 FQ？ a.除了Ca 2+通道，阿片类药物调节哪些效应物， GH 3细胞中的FQ？ B.阿片类药物是否通过G蛋白抑制GH 3细胞肌动蛋白原的释放 bg亚单位？ C. L-型钙通道抑制在细胞凋亡中的作用是什么？阿片调节GH 3细胞催乳素释放？ 4.特异性Ca 2+通道亚型是否在以下中枢作用中发挥作用：阿片类药物和FQ？ a.α 10亚基（或其他阿片类和阿片肽敏感亚基）在中枢神经元中与阿片样物质和/或ORL-1受体共表达？ B.特异性Ca 2+通道亚型是否参与阿片样物质和/或多巴胺在奖赏通路中的释放受FQ调节吗？

英文摘要

Mechanisms and Importance of Opioid and ORL-1 Receptor Coupling to Ca2+ Channel Subtypes 1. What are the molecular identities of opioid and orphanin FQ-sensitive Ca2+ channel subtypes? a. Do ORL- 1 receptors couple like opioid receptors to L-type Ca2+ channels when expressed in GH3 cells? b. Which different L-type Ca2+ channel a1 subunit transcripts are expressed by GH3 cells? c. Do antisense oligonucleotides to the a1 subunit abolish the opioid- and orphanin-sensitive Ca2+ current component? d. Do opioid and ORL-1 receptors expressed in HEK293 cells couple to Ca2+ channels formed by a10 subunits? 2. What G protein mechanisms couple opioid and ORL-1 receptors to CA2+ channels? a. Is there a consensus sequence at which bg binds to all opioid and orphanin FQ regulated Ca2+ channels? b. Does a peptide mimicking this sequence prevent receptor coupling to L- type Ca2+ channels in GH3 cells? c. Can a similar approach uncouple opioid receptors from a1a, a1b and a1d Ca2+ channels in HEK293 cells? 3. What is the contribution of L-type Ca2+ channels, relative to other effectors, in the modulation of vesicular release by opioids and orphanin FQ? a. Other than Ca2+ channels, what effectors are regulated by opioids and orphanin FQ in GH3 cells? b. Do opioids inhibit pro[actin release from GH3 cells through G protein bg subunits? c. What is the contribution of L-type Ca2+ channel inhibition in the opioid regulation of prolactin release from GH3 cells? 4. Do specific Ca2+ channel subtypes have a role in the central actions of opioids and orphanin FQ? a. Are a10 subunits (or other opioid and orphanin FQ sensitive subunits) coexpressed with opioid and/or ORL-1 receptors in central neurons? b. Do specific Ca2+ channel subtypes participate in the opioid and/or orphanin FQ regulation of dopamine release in the reward pathway?

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