Endomorphin analogues containing D‐Pro2 discriminate different μ‐opioid receptor mediated antinociception in mice
Endomorphin analogues containing D‐Pro2 discriminate different μ‐opioid receptor mediated antinociception in mice
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DOI：
10.1038/sj.bjp.0705047
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发表时间：
2002-12
影响因子：
7.3
通讯作者：
S. Sakurada;Hiroyuki Watanabe;Takafumi Hayashi;M. Yuhki;T. Fujimura;K. Murayama;C. Sakurada;T. Saku
中科院分区：
文献类型：
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作者：
S. Sakurada;Hiroyuki Watanabe;Takafumi Hayashi;M. Yuhki;T. Fujimura;K. Murayama;C. Sakurada;T. Saku
在小鼠上研究了D-Pro2-内吗啡对内吗啡抑制缩足反应的拮抗作用。鞘内注射D-Pro2-内吗啡-1和d-Pro2-内吗啡-2单独对伤害性温度阈值无显著影响。同时注射D-Pro2-内吗啡素-1(0.05-0.1pmo1)。内吗啡-1(5.0nmol)或内吗啡-2(5.0nmol)可显著减少内吗啡-1的抗伤害作用，而内吗啡-2的抗伤害作用不受内吗啡-Pro2-内吗啡-1的影响。其类似物D-Pro2-内吗啡-2(100pmoL)显著降低内吗啡-2(5.0nmoL)，但byD‐Pro2‐endomorphin‐1.D‐Pro2‐endomorphin‐1.D‐Pro2‐endomorphin‐1不能拮抗I.T.的抗伤害效应。μ阿片受体激动剂DAMGO，而D-Pro2-内吗啡-2不能减弱DAMGO的作用。这些结果表明，含有D-Pro2的内吗啡类似物能够在脊髓水平区分μ1-和μ2-阿片受体激动剂的抗伤害作用。DOI：10.1038/sj.bjp.0705047
The antagonistic actions ofD‐Pro2‐endomorphins on inhibition of the paw withdrawal response by endomorphins were studied in mice.D‐Pro2‐endomorphin‐1 andD‐Pro2‐endomorphin‐2, injected intrathecally (i.t.), had no significant effect on the nociceptive thermal threshold alone. WhenD‐Pro2‐endomorphin‐1 (0.05–0.1 pmol) was injected simultaneously with i.t. endomorphin‐1 (5.0 nmol) or endomorphin‐2 (5.0 nmol), antinociception induced by endomoprhin‐1 was reduced significantly, whereas endomorphin‐2‐induced antinociception was not affected byD‐Pro2‐endomorphin‐1. Antinociception induced by i.t. endomorphin‐2 (5.0 nmol) was reduced significantly by its analogue,D‐Pro2‐endomorphin‐2 (100 pmol), but not byD‐Pro2‐endomorphin‐1.D‐Pro2‐endomorphin‐1.D‐Pro2‐endomorphin‐1 also antagonized the antinociceptive effect of i.t. DAMGO, a μ‐opioid receptor agonist, whereasD‐Pro2‐endomorphin‐2 failed to reduce the effect of DAMGO. These results suggest that endomorphin analogues containingD‐Pro2are able to discriminate the antinociceptive actions of μ1‐ and μ2‐opioid receptor agonists at the spinal cord level.British Journal of Pharmacology(2002)137, 1143–1146. doi:10.1038/sj.bjp.0705047