Different mechanism of the antinociceptive effects of morphine and dermorphin tetrapeptide analogs

吗啡和皮吗啡四肽类似物抗伤害作用的不同机制

• 批准号: 06672275
• 负责人: SAKURADA Shinobu
• 金额: $ 1.41万
• 依托单位: Tohoku College of Pharmacy
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06672275/
• 关键词: Morphine; Dermorphin; mu1 receptor subtype; Chemical noxious stimulus; Mechanical noxious stimulus; Naloxonazine; morphine; dermorphin; μ_1受容体; μ_2受容体; 化学的侵害刺激; 機械的侵害刺激; naloxonazine; β-funaltrexamine; μ受容体; μ2受容体; β-funaltraxamine

1) We investigated the role of mu1-opioid receptors on morphine-and dermorphin tetrapeptide analogs-induced antinociception using supraspinally mediated behavours exclusive of the spinal reflex as criteria in mice.2) Both intracerebroventricular (i.c.v.) and intrathecal (i.t.) administered morphine produced potent and significant antinociceptive activity in the tail-pressure test as a mechanical noxious stimulus. The pretreatment with naloxonazine failed to antagonize the activity.3) In the formalin test as a chemical noxious stimulus, licking and biting response was significantly inhibited by both i.c.v. and i.t. administered morphine. The activity was remarkably diminished by naloxonazine.4) In the hot plate test as a thermal noxious stimulus, both i.c.v. and i.t. administered-morphine induced antiniciceptive activity was significantly reduced by the pretreatment with naloxonazine.5) Pretreatment with naloxonazine antagonized the antinociceptive effects of both i.c.v. and i.t. dermorphin tetrapeptide analog (H-Tyr-DArg-Phe-beta-ala : TAPA) against response to mechanical and chemical stimuli.6) Although the pretreatment with naloxonazine was not antagonized the antinociceptive activity of i.c.v. TAPA-NH2 to both mechanical and chemical noxious stimuli and i.t. TAPA-NH2 to mechanical noxious stimulus, i.t. TAPA-NH2-induced antinociception to chemical stimulus was significantly reduced by naloxonazine.

1) 我们以小鼠中不包括脊髓反射的脊髓上介导的行为为标准，研究了 mu1-阿片受体对吗啡和皮吗啡四肽类似物诱导的镇痛作用的作用。 2) 脑室内 (i.c.v.) 和鞘内 (i.t.) 给药的吗啡在小鼠中产生了有效且显着的镇痛活性。 尾部压力测试作为机械有害刺激。纳洛嗪预处理未能拮抗该活性。3）在作为化学毒性刺激的福尔马林试验中，舔和咬反应被静脉注射和注射显着抑制。和它。给予吗啡。纳洛嗪显着降低了活性。4) 在作为热伤害刺激的热板测试中，两种 i.c.v.和它。纳洛嗪预处理显着降低吗啡诱导的镇痛活性。5)纳洛嗪预处理拮抗两种静脉注射的镇痛作用。和它。 dermorphin 四肽类似物 (H-Tyr-DArg-Phe-beta-ala : TAPA) 对抗机械和化学刺激的反应。6) 尽管纳洛嗪预处理并未拮抗 i.c.v. 的抗伤害活性。 TAPA-NH2 对机械和化学有害刺激和 i.t. TAPA-NH2 对机械性有害刺激，i.t.纳洛嗪显着降低 TAPA-NH2 诱导的化学刺激抗伤害作用。