OPIOIDS AND CELLULAR SURVIVAL

该项目研究了生理效应， δ阿片类药物作用的潜在生化机制 肽和相关蛋白质HIT（冬眠诱导触发物） 在组织存活中。在本财政年度，我们发现，在孤立的兔子， 心脏制备，其中心脏经受18小时的整体 缺血，DADLE大大提高了功能恢复， 心肌功能DADLE的此操作被 选择性δ 2阿片受体拮抗剂。我们还要 DADLE的组织保护作用 通过检查外周系统到中枢神经系统， DADLE可能保护甲基苯丙胺（METH）诱导的 小鼠脑内多巴胺能（DA）神经元损伤。结果 表明DADLE剂量依赖性地阻断了MET诱导的 DA损伤。DADLE的这种作用可能与阿片受体有关 阿片拮抗剂纳洛酮部分逆转了 爸爸。我们还发现DADLE是一种抗氧化剂， 体外，这表明DADLE作为保护性的一部分， 抗MET诱导的DA神经元损伤的药物可能涉及 螯合自由基，已知自由基在 甲基苯丙胺神经毒性。

This project examines the physiological effects and the underlying biochemical mechanisms of action of delta opioid peptides and a related protein HIT (Hibernation Induction Trigger) in tissue survival. In this fiscal year, we found that in isolated rabbit heart preparation in which hearts were subjected to 18 hrs of global ischemia, DADLE greatly enhances the functional recovery of myocardial functions. This action of DADLE is blocked by the selective delta2 opioid receptor antagonist. We also extend our finding on the tissue protective property of DADLE from the peripheral system to the central nervous system by examining if DADLE might protect against methamphetamine(METH)-induced dopaminergic (DA) neuronal damage in mouse brain. Results indicate that DADLE dose-dependently blocks the METH-induced DA damage. This action of DADLE may involves opioid receptors as opioid antagonist naltrexone partially reverses this action of DADLE. We also found that DADLE is an antioxidative agent in vitro, suggesting that part of the ation of DADLE as a protective agent against METH-induced DA neuronal damage may involve a sequestration of free radicals which are known to play a role in METH neurotoxicity.