Shibata S, Tominaga K, Watanabe S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Eur J Pharmacol. 1995 Jun 12;279(2-3):197-202. doi: 10.1016/0014-2999(95)00152-b.
We examined the effects of mu-opioid receptor agonist and antagonists, and kappa-opioid receptor agonist on the hypoxia/hypoglycemia-induced reduction in 2-deoxyglucose uptake of rat hippocampal slices. Naloxone, a mu-opioid receptor antagonist and (5,7,8)-(+)-3,4-dichloro-N-methyl-N-(7,8,1-pyrrolidinyl)-1-oxaspirol+ ++ (4,5)dec-8-yl)-benzeneacetamide methanesulfonate, U-62,066E, a kappa-opioid receptor receptor agonist, showed neuroprotective actions against the hypoxia/hypoglycemia-induced deficit in glucose uptake. In contrast, morphine exhibited an exacerbating action. These results suggest that blockade of mu-opioid receptor- and stimulation of kappa-opioid receptor-mediated functions has a protective role against the hypoxia/hypoglycemia-induced decreases in glucose metabolism in hippocampal slices. Chronic administration of morphine (10 mg/kg) for 9 days affected neither the basal nor the hypoxia/hypoglycemia-induced reduction in 2-deoxyglucose uptake. Rats treated with morphine chronically exhibited not only tolerance to the analgesic effect but also tolerance to the exacerbating action. However, chronic morphine did not modify U-62,066E-induced neuroprotection. These findings indicate that the receptor mechanisms of neuroprotection produced by the activation of kappa-opioid receptors may not be involved in mu-opioid receptor function.
我们研究了μ-阿片受体激动剂和拮抗剂以及κ-阿片受体激动剂对缺氧/低血糖诱导的大鼠海马切片2-脱氧葡萄糖摄取减少的影响。μ-阿片受体拮抗剂纳洛酮以及κ-阿片受体激动剂(5,7,8)-(+)-3,4-二氯-N-甲基-N-(7,8,1-吡咯烷基)-1-氧杂螺[4.5]癸-8-基)-苯乙酰胺甲磺酸盐（U-62,066E）对缺氧/低血糖诱导的葡萄糖摄取缺陷具有神经保护作用。相比之下，吗啡则表现出加剧作用。这些结果表明，阻断μ-阿片受体介导的功能和刺激κ-阿片受体介导的功能对缺氧/低血糖诱导的海马切片葡萄糖代谢降低具有保护作用。连续9天给予吗啡（10mg/kg）既不影响基础状态下的2-脱氧葡萄糖摄取，也不影响缺氧/低血糖诱导的摄取减少。长期接受吗啡治疗的大鼠不仅对镇痛作用产生耐受性，而且对加剧作用也产生耐受性。然而，慢性吗啡并未改变U-62,066E诱导的神经保护作用。这些发现表明，κ-阿片受体激活产生神经保护作用的受体机制可能与μ-阿片受体功能无关。
