STUDY ON ELUCIDATION OF ACTION MECHANISM OF OPIOID PEPTIDES,DYNORPHINS

阿片肽、强啡肽作用机制阐明的研究

• 批准号: 09672340
• 负责人: HIRAMATSU Masayuki
• 金额: $ 2.18万
• 依托单位: MEIJO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672340/
• 关键词: DYNORPHIN; KAPPA-OPIOID RECEPTOR; CARBON MONOXICE-INDUCED AMNESIA; CARBACHOL; CHOLINERGIC MEURONAL SYSTEM; HIPPOCAMPUS; LEARNING AND MEMORY; ACETYLCHOLINE; 脳内微量透析法

The aim of the present study was to elucidate physiological roles of kappa opioid receptor agonists in the learning and memory process, using behavioral and neurochemical procedures. 1) U-50, 488H and dynorphin A (1-13), kappa opioid receptor agonists, improved carbachol-induced impairment of learning and memory in mice and rats in the passive avoidance task. 2) U-50, 488H improved scopolamine- and mecamylamine-induced impairment of learning and memory in the passive avoidance task. 3) Perfusion of carbachol or mecamylamine decreased the extracellular acetyicholine concentration in the rat hippocampus using a microdialysis technique. Dynorphin A (1-13) and U-50, 488H inhibited this decrease in acetyicholine, and nor-BNI, a selective kappa opioid receptor antagonist, prevented these effects. These results suggest that improving effects of kappa opioid receptor agonists on impairment of learning and memory accompanied with improvement of decrease in acetyicholine release in the hippocampus.

本研究的目的是使用行为和神经化学程序阐明卡帕阿片受体激动剂在学习和记忆过程中的生理作用。 1）U-50，488H和Dynorphin A（1-13），Kappa阿片受体激动剂，在被动避免任务中，Carbachol诱导的小鼠和大鼠的Carbachol诱导的学习和记忆障碍。 2）U-50，488H改善了被动避免任务中的scopolamine-和mecamylamine诱导的学习和记忆障碍。 3）使用微透析技术，灌注卡巴醇或美甲基胺可降低大鼠海马中的细胞外乙酰氨酸浓度。 Dynorphin A（1-13）和U-50，488H抑制了乙乙酸酯的减少，而选择性Kappa阿片类受体拮抗剂Nor-Bni则阻止了这些作用。这些结果表明，改善Kappa阿片类药物激动剂对学习和记忆障碍的影响，并伴随着海马中乙炔酸释放的减少。

项目成果

M.Hiramatsu and T.Kameyama: "Roles of kappa-opioid receptor agonists in learning and memory impairment in animal models" Meth.Find.Exp.Chin.Pharmacol.20(7). 595-599 (1998)

M.Hiramatsu 和 T.Kameyama：“κ-阿片受体激动剂在动物模型学习和记忆障碍中的作用”Meth.Find.Exp.Chin.Pharmacol.20(7)。

M.Hiramatsu, T.Hyodo and T.Kameyama: "U-50488H,a selective kappa-opioid receptor agonist, ameliorates memory impairments induced by muscarinic autoreceptor agonist, carbachol in mice" Neurosci.Lett.236. 45-48 (1997)

M.Hiramatsu、T.Hyodo 和 T.Kameyama：“U-50488H，一种选择性 kappa-阿片受体激动剂，可改善小鼠体内由毒蕈碱自身受体激动剂卡巴胆碱引起的记忆障碍” Neurosci.Lett.236。

M.Hiramatsu, T.Kameyama: "Roles of κ-opioid receptor agonists in learning and memory inpairment in animal models" Meth.Find.Exp.Clin.Pharmacol.20 (7). 595-599 (1998)

M.Hiramatsu、T.Kameyama：“κ-阿片受体激动剂在动物模型学习和记忆障碍中的作用”Meth.Find.Exp.Clin.Pharmacol.20 (7) (1998)。

M.Hiramatsu: "Reversion of muscarinic autoreceptor agonist-induced acetylcholine decrease and learning impairment by dynorphin A(1-13),an endogenous κ-opioid receptor agonist" Brit.J.Pharmacol.123. 920-926 (1998)

M. Hiramatsu：“强啡肽 A(1-13)（一种内源性 κ-阿片受体激动剂）可逆转毒蕈碱自身受体激动剂诱导的乙酰胆碱减少和学习障碍”Brit.J.Pharmacol.123 (1998)。

M.Hiramatsu, M.Murai, T.Kameyama: "Different modulation of cholinergic neuronal systems by dynorphin A (1-13) in carbon monoxide-exposed mice" Biochem.Pharmacol.57. in press (1999)

M.Hiramatsu、M.Murai、T.Kameyama：“在一氧化碳暴露小鼠中强啡肽 A (1-13) 对胆碱能神经元系统的不同调节”Biochem.Pharmacol.57。