DRUG RECEPTORS, NEUROTRANSMITTERS AND ADDICTION

药物受体、神经递质和成瘾

• 批准号: 3853711
• 负责人: M J KUHAR
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3853711
• 关键词: NMDA receptors; PCP receptor; cocaine; dorsal root; drug addiction; drug receptors; laboratory rat; neurotransmitters; opioid receptor; phencyclidine; protein transport; receptor binding; vagus nerve

This project focuses on various drugs of abuse and the receptors with which they interact. We completed a study examining the binding of PCP and related compounds at the cocaine receptor. The relative potencies of these compounds were such that some of the behavioral effects of PCP might be related to its action at the cocaine receptor; in other words, the affinity of PCP at the cocaine binding site was interesting but considerably less than its affinity at its own receptor. (Ki of 1.59 mM vs a Ki of about 0.12 mM). Thus, at high blood levels, PCP could interact with the cocaine receptor but it would most likely occupy the PCP site at the NMDA receptor at much lower concentrations. Another study examined the movement of opiate receptors within neurons. Receptors are synthesized by the usual protein synthetic machinery of cells. They are then transported to sites and inserted into the membrane. We examined the transport of opiate receptors in rat vagus and in dorsal roots of spinal nerves. We found that the opiate receptors were transported in these neurofibers by fast transport and this agrees with many studies of other receptors. The binding sites in the axons had properties similar to those for receptors observed in brain tissue; the binding sites had appropriate pharmacology, were GTP sensitive as well as showed effects of sodium.

这个项目关注的是各种滥用药物和受体 它们相互作用。我们完成了一项研究，考察了五氯酚的结合情况 以及可卡因受体上的相关化合物。的相对效力 这些化合物使得五氯苯酚的一些行为影响 可能与它在可卡因受体上的作用有关；换句话说， 五氯酚在可卡因结合部位的亲和力很有趣，但 大大低于它在自身受体上的亲和力。(KI为1.59 mm vs KI约为0.12毫米)。因此，在血液水平较高时，五氯苯酚可以与 可卡因受体，但它很可能占据PCP的位置 NMDA受体的浓度要低得多。 另一项研究检测了阿片受体在神经元内的运动。 受体是由常见的蛋白质合成机制合成的 细胞。然后，它们被运输到部位并插入膜中。 我们研究了阿片受体在大鼠迷走神经和背侧的转运。 脊神经的根。我们发现阿片受体是 通过快速运输在这些神经纤维中运输，这与 对其他受体的许多研究。轴突中的结合部位有 类似于在脑组织中观察到的受体的特性； 结合部位有适当的药理作用，对GTP也敏感吗 如显示的钠的影响。