Qi J A, Mosberg H I, Porreca F
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson 85724.
Life Sci. 1990;47(11):PL43-7. doi: 10.1016/0024-3205(90)90545-3.
The present study has characterized the antinociceptive actions of [D-Ala2]deltorphin II following intracerebroventricular (i.c.v.) administration in the mouse tail-flick test. [D-Ala2]deltorphin II produced dose- and time-related antinociception, with maximal effects at +10 min and significant antinociception which lasted for 40-60 min. [D-Ala2]deltorphin II was 13-fold more potent than i.c.v. [D-Pen2, D-Pen5]enkephalin (DPDPE), a second highly selective delta agonist, and approximately equipotent with i.c.v. morphine in producing antinociception. The antinociceptive effects of i.c.v. [D-Ala2]deltorphin II and DPDPE, but not those of morphine, were antagonized by the selective delta antagonist, ICI 174,864. In contrast, pretreatment with the non-equilibrium mu antagonist, beta-funaltrexamine blocked morphine antinociception, but failed to antagonize [D-Ala2]deltorphin II and DPDPE antinociception. These data indicate that [D-Ala2]deltorphin II produced its antinociceptive effects at a supraspinal delta receptor. [D-Ala2]deltorphin II appears to be the most appropriate delta opioid agonist currently available for studies in vivo and support the involvement of delta receptors in supraspinal antinociception.
本研究已对[D - Ala2]强啡肽II在小鼠甩尾试验中脑室内（i.c.v.）给药后的抗伤害感受作用进行了表征。[D - Ala2]强啡肽II产生了剂量和时间相关的抗伤害感受作用，在+10分钟时达到最大效应，且显著的抗伤害感受作用持续40 - 60分钟。[D - Ala2]强啡肽II的效力比脑室内注射的[D - Pen2, D - Pen5]脑啡肽（DPDPE，另一种高度选择性的δ激动剂）强13倍，并且在产生抗伤害感受方面与脑室内注射的吗啡大致等效。脑室内注射[D - Ala2]强啡肽II和DPDPE的抗伤害感受作用，但吗啡的抗伤害感受作用则不然，被选择性δ拮抗剂ICI 174,864拮抗。相反，用非平衡μ拮抗剂β - 芬太尼丁预处理可阻断吗啡的抗伤害感受作用，但未能拮抗[D - Ala2]强啡肽II和DPDPE的抗伤害感受作用。这些数据表明，[D - Ala2]强啡肽II在脊髓上的δ受体处产生其抗伤害感受作用。[D - Ala2]强啡肽II似乎是目前可用于体内研究的最合适的δ阿片类激动剂，并支持δ受体参与脊髓上的抗伤害感受作用。
