NEUROPEPTIDES RECEPTORS

我们的长远目标是：为了表征神经递质 受体及其参与精神药理学机制 代理人，以及II.研究信息中的感受器后事件 转移和对连续给药的适应性反应 如受体耐受性和阿片依赖性。 所以具体 今后五年的目标将分为两大类： I. P物质受体项目。 由于P物质广泛存在于 分布在中枢神经系统，有迹象表明它参与了 几个功能和抗抑郁药的影响，我们将 研究1）不同SP受体的一般特性 亚型和SP受体相关GTP结合调节的作用 蛋白 2)SP受体阳性神经元与 抗抑郁药和其他神经系统。 二.阿片类药物耐受性和依赖性项目。 我们会研究 阿片类药物耐受性和依赖性的生物化学相关性 神经母细胞瘤×神经胶质瘤（NG 108 -15）模型系统对阿片类药物的作用 受体-腺苷酸环化酶复合物和GTP结合调节 将受体与腺苷酸环化酶偶联的蛋白质。 具体目标 将确定1）阿片类药物是否会对抑制性 GTP结合蛋白或阿片受体，这可能解释了一些 宽容的机制。 2)是否代偿性肥大的 阿片类药物产生的腺苷酸环化酶与任何定性或 刺激性GTP结合蛋白的定量修饰。 3)到 检查NG 108 -15长期暴露是否出现任何变化 在阿片耐受/依赖大鼠中也观察到细胞对阿片的依赖性。

Our long term objectives are: I. To characterize neurotransmitter receptors and their involvement in the mechanisms of psychopharmacologic agents, and II. To study postreceptor events involved in information transfer and in the adaptive responses to continuous drug administration such as receptor tolerance and opiate dependence. Therefore, the specific aims for the next five years will be divided in two main groups: I. Project on the Substance P Receptors. Since substance P is widely distributed in the CNS and there are indications of its involvement in several functions and in the effects of antidepressant agents, we will investigate 1) the general characteristics of the different SP receptor subtypes and the role of the SP receptor associated GTP-binding regulatory protein. 2) the relationship of SP receptor-containing neurons with antidepressant agents and with other neuronal systems. II. Project on Opiate Tolerance and Dependence. We will examine the biochemical correlates of opiate tolerance and dependence in the neuroblastoma x glioma (NG108-15) model system on the opioid receptor-adenylate cyclase complex and in the GTP-binding regulatory proteins that couple receptors to the adenylate cyclase. The specific aims will determine 1) whether opiates produce any alteration on the inhibitory GTP-binding protein or in the opiate receptor that may explain some of the mechanisms of tolerance. 2) Whether the compensatory hypertrophy of the adenylate cyclase produced by opiates is correlated to any qualitative or quantitative modification of the stimulatory GTP binding protein. 3) To examine if any of the changes seen with prolonged exposure of NG108-15 cells to opiates is also seen in opiate tolerant/dependent rats.