the role of mu-opioid receptor subtypes on antinociception of mu-opioid receptor agonists

mu-阿片受体亚型对 mu-阿片受体激动剂抗伤害作用的作用

• 批准号: 12672220
• 负责人: SAKURADA Shinobu
• 金额: $ 2.24万
• 依托单位: Tohoku Parmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672220/
• 关键词: mu-opioid receptor antagonist; mu1-opioid receptor; mu2-opioid receptor; endomorphin-1; endomorphin-2; naloxonazine; β-funaltrexamine; D-Pro^2-endomorphins; D-Pro-endomorphin-1; D-Pro-endomorphin-2; DAMGO; μ opioid; 3-methoxynaltorexone

At least two mti-oploid receptor subtypes have been proposed; mul-and mu2-opioid rceptor subtypes. β-funaltrexamine irreversibly antagonizes both mul-and mu2-oploid receptors, whereas naloxonazine selectively antagonizes the mul-oplold receptor. However, the selective mu2-opioid antagonist has not yet been found. We found that D-Pro^2-endomorphin-1 selectively blocked the antinociceptive effect of i.t. administered DAMGO, as well as endomorphin-1, whereas antln6ciceptlon of Tyr-D-Arg-Phe-p-AJa, or endomorphin-2 was InhibIted by co-administration of D-Pro but not D-Pro Theses results indicate that these rwo D-Pro^2-endomorphins may be a useful tool to dlscrimate between the antinociceptive effects of mul-and mu2-oploid receptor agonists.

至少有两种多倍体受体亚型被提出；mu1和mu2阿片受体亚型。β-富纳曲胺不可逆地拮抗多倍体和多倍体受体，而纳洛嗪选择性拮抗多倍体受体。然而，选择性的mu2-阿片拮抗剂尚未被发现。我们发现D-Pro^2-内啡肽-1选择性地阻断了单药给药DAMGO和内啡肽-1的抗伤害性作用，而同时给药D-Pro - d - arg - ph -p- aja或内啡肽-2的抗伤害性作用被D-Pro抑制，但不被D-Pro抑制。这些结果表明，这两种D-Pro^2-内啡肽可能是描述mu2和mu2-oploid受体激动剂的抗伤害性作用的有用工具。

项目成果

Fukie Niijima.Koichi Tan-No, Akihisa Esashi, Osamu Nakagawasai, Takeshi Tadano, Norio Takahashi, Akihiko Yonezawa, Shinobu Sakurada, Kensuke Kisara: "Inhibitory effect of intracerebroventricularly-admninistered [D-Arg^2,β-Ala^4]-dermorphin (1-4) on gastro

Fukie Niijima.Koichi Tan-No、Akihisa Esashi、Osamu Nakakawasai、Takeshi Tadano、Norio Takahashi、Akihiko Yonezawa、Shinobu Sakurada、Kensuke Kisara：“脑室内给药的抑制作用[D-Arg^2,β-Ala^4]-皮吗啡 (1-4) 对胃的影响

Shinobu Sakurada: "Endomorphin analogues containing D-Pro^2 discriminate different μ-opioid receptor mediated antinociception in mice"Brit.J.Pharmacol. 1143-1146 (2002)

Shinobu Sakurada：“含有 D-Pro^2 的内吗啡类似物可区分小鼠中不同的 μ-阿片受体介导的抗镇痛作用”Brit.J.Pharmacol 1143-1146 (2002)

Shinobu Sakurada: "Synthesis and structure-activity relationships of an orally-available and long-acting analgesic peptide, N^α-amidino-Tyr-D-Arg-Phe-MeβAla-OH (ADAMB)"J. Med. Chem. 45. 5081-5089 (2002)

Shinobu Sakurada：“口服长效镇痛肽 N^α-脒基-Tyr-D-Arg-Phe-MeβAla-OH (ADAMB) 的合成及其结构-活性关系”J. Med。 .5081-5089 (2002)

Shinobu Sakurada: "D-Pro^2-andomorphin-1 and D-Pro^2-endomorphin-2, respectively, attenuate the antinociception induced by encomorphin-1 and endomorphin-2 given intrathecally in the mouse"J.Pharmacol.Exp.Ther.. 303. 874-879 (2002)

Shinobu Sakurada：“D-Pro^2-andomorphin-1 和 D-Pro^2-endomorphin-2 分别减弱小鼠鞘内给予 encomorphin-1 和 endomorphin-2 引起的镇痛作用”J.Pharmacol.Exp。

Minoru Narita, Shinobu Sakurada: "Recent Advances In the Search for the μ-OpioidergiF System"Jpn.J.Pharmacol.. 89. 201-202 (2002)

Minoru Narita、Shinobu Sakurada：“μ-OpioidergiF 系统研究的最新进展”Jpn.J.Pharmacol.. 89. 201-202 (2002)