DEXTRORPHAN AS A PROBE FOR RECOMBINANT NMDA RECE

右旋啡烷作为重组 NMDA RECE 的探针

• 批准号: 2700826
• 负责人: JANE E ISHMAEL
• 金额: $ 3.17万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-11 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2700826
• 关键词: NMDA receptors; inhibitor /antagonist; mutant; receptor binding; recombinant proteins; tissue /cell culture; transfection

Dextrorphan is a selective noncompetitive antagonist of the N-methyl- D-aspartate (NMDA) subfamily of glutamate receptors. Like other ligand-activated ion channels, the NMDA receptor appears to be composed of several subunits which co-assemble to form a functional channel. The specific aims of the projected research are to (1) identify the subunit of the NMDA receptor with which [3H]dextrorphan interacts and (2) to elucidate the specific structural domains responsible for the interaction of [3H]dextrorphan with the NMDA receptor-operated ion channel. Radioligand binding studies will be used to characterize [3H]dextrorphan binding in membrane preparations derived from COS cells transiently transfected with wild-type and mutant recombinant NMDA receptor constructs. In addition, immunologic techniques will be used to confirm both expression and co-assembly of the various subunits in COS cell membranes. Although the research goals of this project are to characterize the structural determinants responsible for the interaction of [3H]dextrorphan with recombinant NMDA receptors, an overall objective of the proposed research is to provide a more complete mechanistic understanding of the functional significance of various combinations of NMDA receptor subunits. In turn, these studies may provide useful insights into the molecular basis for the psychotomimetic properties of noncompetitive NMDA antagonists as well as the therapeutic potential of these compounds to reduce neuronal injury associated with stroke, head trauma, hypoglycemia and sustained convulsions.

右啡烷是 N-甲基- 的选择性非竞争性拮抗剂 D-天冬氨酸 (NMDA) 谷氨酸受体亚家族。和其他人一样 配体激活的离子通道，NMDA 受体似乎是 由多个亚基组成，这些亚基共同组装形成功能性的 渠道。预计研究的具体目标是（1） 鉴定 NMDA 受体的亚基，[3H]右啡烷 相互作用并（2）阐明特定的结构域 负责[3H]右啡烷与 NMDA 的相互作用 受体操纵的离子通道。放射性配体结合研究将 用于表征膜制剂中[3H]右啡烷的结合 源自瞬时转染野生型和 突变重组 NMDA 受体构建体。此外，免疫学 技术将用于确认表达和共同组装 COS 细胞膜中的各种亚基。虽然研究 该项目的目标是描述结构性决定因素 负责[3H]右啡烷与重组体的相互作用 NMDA 受体，拟议研究的总体目标是 提供对功能的更完整的机械理解 NMDA 受体亚基的各种组合的意义。在 反过来，这些研究可能为分子生物学提供有用的见解 非竞争性 NMDA 拟精神病特性的基础 拮抗剂以及这些化合物的治疗潜力 减少与中风、头部外伤相关的神经元损伤， 低血糖和持续抽搐。