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中枢μ-阿片系统参与小鼠的搔抓行为以及κ-阿片系统激活对其的抑制作用。

Involvement of central mu-opioid system in the scratching behavior in mice, and the suppression of it by the activation of kappa-opioid system.

作者信息

Umeuchi Hideo, Togashi Yuko, Honda Toshiyuki, Nakao Kaoru, Okano Kiyoshi, Tanaka Toshiaki, Nagase Hiroshi

机构信息

Pharmaceutical Research Laboratories, Toray Industries, Inc, 1111 Tebiro Kamakura, Kanagawa 248-8555, Japan.

出版信息

Eur J Pharmacol. 2003 Sep 5;477(1):29-35. doi: 10.1016/j.ejphar.2003.08.007.

Abstract

The role of central mu- and kappa-opioid receptors in the regulation of itch sensation was examined using pruritogen-induced mouse scratching behavior model. Intracerebroventricular administration of beta-funaltrexamine, a selective mu-opioid receptor antagonist, inhibited the scratching behavior induced by intradermal substance P, but subcutaneous administration of beta-funaltrexamine did not. Similarly, the scratching inhibitory activity of subcutaneously administered TRK-820, (-)-17-(cyclopropylmethyl)-3, 14beta-dihydroxy-4, 5alpha-epoxy-6beta-[N-methyl-trans-3-(3-furyl) acrylamido] morphinan hydrochloride, a kappa-opioid receptor agonist, was antagonized by intracerebroventricular administration of nor-binaltorphimine (10 microg/site), a kappa-opioid receptor antagonist, but was not by subcutaneous administration of nor-binaltorphimine. In addition, the scratching induced by the direct activation of central mu-opioid receptor by intracisternal morphine was significantly and dose-dependently inhibited by subcutaneous administration of TRK-820. Taken all together, it is suggested that the central mu-opioid receptors play a role in the processing of itch sensation, and the activation of central kappa-opioid receptors antagonize the central mu-opioid receptor mediated itch processing, thereby suppressing itch sensation.

摘要

利用致痒原诱导的小鼠搔抓行为模型,研究了中枢μ-和κ-阿片受体在瘙痒感觉调节中的作用。脑室内注射选择性μ-阿片受体拮抗剂β-芬太尼环唑抑制了皮内注射P物质诱导的搔抓行为,但皮下注射β-芬太尼环唑则没有。同样,皮下注射κ-阿片受体激动剂TRK-820(盐酸盐,(-)-17-(环丙基甲基)-3,14β-二羟基-4,5α-环氧-6β-[N-甲基反式-3-(3-呋喃基)丙烯酰胺基]吗啡喃)的搔抓抑制活性,被脑室内注射κ-阿片受体拮抗剂nor-纳洛酮啡(10微克/部位)所拮抗,但皮下注射nor-纳洛酮啡则没有。此外,脑池内注射吗啡直接激活中枢μ-阿片受体所诱导的搔抓,被皮下注射TRK-820显著且剂量依赖性地抑制。综上所述,提示中枢μ-阿片受体在瘙痒感觉的处理中起作用,中枢κ-阿片受体的激活拮抗中枢μ-阿片受体介导的瘙痒处理,从而抑制瘙痒感觉。

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