Shibata S, Tominaga K, Watanabe S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Neurosci Lett. 1994 Dec 5;182(2):155-8. doi: 10.1016/0304-3940(94)90786-2.
The aim of the present study was to determine whether U-50,488H and U-62,066E, kappa-opioid receptor agonists cause a neuroprotective action against hypoxia/hypoglycemia-induced reduction in 2-deoxyglucose (2-DG) uptake of hippocampal slices from U-50,488H-tolerant rats. Both U-50,488H and U-62,066E exhibited an attenuating effect on hypoxia/hypoglycemia-induced reduction in 2-DG uptake of hippocampal slices. Hypoxia/hypoglycemia-induced deficit of 2-DG uptake was prevented by cotreatment with naloxone, an opioid receptor antagonist, but potentiated by cotreatment with morphine, a mu-opioid receptor agonist. Chronic administration of U-50,488H resulted in the development of tolerance to the analgesic effect as well as the neuroprotective effect whereas this treatment affected neither basal- nor hypoxia/hypoglycemia-induced decreases in 2-DG uptake. Chronic administration of U-50,488H did not modify naloxone-induced attenuation of 2-DG uptake deficit but slightly potentiated the morphine-induced exacerbation. These findings suggest that the tolerance to kappa-opioid receptors does not affect the mu-opioid receptor-mediated neuroprotective or neurotoxic action.
本研究的目的是确定κ-阿片受体激动剂U-50,488H和U-62,066E是否对缺氧/低血糖诱导的U-50,488H耐受大鼠海马切片2-脱氧葡萄糖（2-DG）摄取减少具有神经保护作用。U-50,488H和U-62,066E均对缺氧/低血糖诱导的海马切片2-DG摄取减少具有减轻作用。阿片受体拮抗剂纳洛酮共处理可预防缺氧/低血糖诱导的2-DG摄取缺陷，而μ-阿片受体激动剂吗啡共处理则会使其增强。长期给予U-50,488H会导致对镇痛作用以及神经保护作用产生耐受性，而这种处理既不影响基础状态下的2-DG摄取减少，也不影响缺氧/低血糖诱导的2-DG摄取减少。长期给予U-50,488H并未改变纳洛酮诱导的2-DG摄取缺陷减轻，但略微增强了吗啡诱导的加剧作用。这些发现表明，对κ-阿片受体的耐受性并不影响μ-阿片受体介导的神经保护或神经毒性作用。
