MECHANISMS & IMPORTANCE OF OPIOID AND ORL1 RECEPTOR COUPLING TO CA2+ CHANNELS

阿片和ORL-1受体与钙离子偶联的机制及意义 通道子类型 1.阿片类药物和孤儿对FQ敏感的分子特征是什么 CA2+通道亚型？ A.ORL-1受体是否像阿片受体一样偶联到L型钙通道 当在GH3细胞中表达时？ B.哪些不同的L型钙通道A1亚单位转录 是由GH3细胞表达的吗？ C.A1亚基的反义寡核苷酸是否能消除阿片类药物--以及 孤儿敏感的钙电流成分？ D.在HEK293细胞中表达的DO阿片和ORL-1受体与钙离子偶联 通道是由A10亚基组成的？ 2.阿片受体和ORL-1受体与钙离子偶联的G蛋白机制 频道？ A.BG与所有阿片类药物和 孤儿FQ对钙通道的调节？ B.模拟此序列的多肽是否阻止受体与L偶联- GH3细胞的钙通道类型？ C.类似的方法能否将阿片受体从A1a、A1b和A1d中分离出来 HEK293细胞的钙通道？ 3.L型钙通道相对于其他钙通道的贡献是什么 阿片类药物和孤儿对囊泡释放的调节作用 FQ？ A.除了钙离子通道外，还有哪些效应器受阿片类药物和 GH3细胞中的孤儿FQ？ B.阿片类药物是否通过G蛋白抑制GH3细胞前肌动蛋白的释放 BG亚基？ C.L型钙通道抑制在大鼠脑缺血再灌注损伤中的作用 阿片类药物对GH3细胞催乳素释放的调节？ 4.特定的钙通道亚型是否在中枢作用中起作用？ 阿片类药物和孤儿FQ？ A.A10亚基(或其他阿片类药物和孤儿FQ敏感亚基) 中枢神经元与阿片和/或ORL-1受体共表达？ B.特定的钙通道亚型是否参与阿片类药物和/或 孤儿FQ对奖赏通路中多巴胺释放的调节？

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?