NEUROPEPTIDES RECEPTORS

我们的长期目标是：一、确定神经递质的特征 受体及其在精神药理学机制中的作用 药物，以及II.研究信息中涉及的受体后事件 持续给药的转移性和适应性反应 如受体耐受性和阿片类药物依赖。因此，具体的 未来五年的目标将分为两大类： I.P物质受体的投射。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 在抗抑郁药的几种作用和效果上，我们会 研究1)不同SP受体的一般特征 SP受体相关GTP结合调节的亚型及其作用 蛋白。2)含SP受体神经元与 抗抑郁剂和其他神经系统。 阿片类药物耐受性和依赖性项目。我们将研究 阿片类药物耐受和依赖的生化相关性 神经母细胞瘤×脑胶质瘤(NG108-15)模型系统对阿片类药物的影响 受体-腺苷环化酶复合体及其在GTP结合调节中的作用 将受体与腺苷环化酶偶联的蛋白质。具体目标 将决定1)阿片类药物是否会对抑制作用产生任何改变 GTP结合蛋白或阿片受体，这可能解释了一些 容忍的机制。2)心脏代偿性肥厚是否 阿片类药物产生的腺苷环化酶与任何质的或 刺激性GTP结合蛋白的定量修饰。3)至 检查长期接触NG108-15是否有任何变化 阿片类药物耐受/依赖大鼠的细胞对阿片类药物的敏感性也很高。

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.