Omega-agatoxin IVA blocks spinal morphine/clonidine antinociceptive synergism.
Omega-agatoxin IVA blocks spinal morphine/clonidine antinociceptive synergism.
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Omega-agatoxin IVA 阻断脊髓吗啡/可乐定镇痛协同作用。
DOI：
10.1016/s0014-2999(96)00561-4
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发表时间：
1996
影响因子：
5
通讯作者：
Howse,KM
中科院分区：
文献类型：
--
作者：
Roerig,SC;Howse,KM
本研究探讨了P型电压依赖性Ca ~（2+）通道参与吗啡或可乐定诱导的脊髓抗伤害作用以及吗啡和可乐定之间的协同作用。鞘内（i.t.）沿着吗啡或可乐定对小鼠的甩尾抗伤害感受增强5-6倍。当吗啡和可乐定同时i.t.给药时，在ω-agatoxin IVA的存在下，相互作用降低为相加作用。在用百日咳毒素（10 ng）预处理的小鼠中，ω-agatoxin IVA没有改变吗啡/可乐定的协同作用。令人惊讶的是，ω-蛇毒素IVA将吗啡耐受小鼠中发生的吗啡/可乐定相互作用逆转为协同作用。这些结果表明，功能性P型钙通道在脊髓吗啡和可乐定的抗伤害性协同作用中起着重要作用。
Involvement of P-type voltage-dependent Ca2+channels in spinal morphine- or clonidine-induced antinociception and in the synergistic interaction between morphine and clonidine was examined in the present studies. Coadministration of the selective P-type antagonist, ω-agatoxin IVA (25 ng) intrathecally (i.t.) to mice along with morphine or clonidine enhanced the tail flick antinociception of each agonist 5–6-fold. The greater-than-additive (synergistic) interaction that occurred when morphine and clonidine were coadministered i.t. decreased to an additive interaction in the presence of ω-agatoxin IVA. In mice pretreated with pertussis toxin (10 ng) to inactivate G proteins, ω-agatoxin IVA did not alter the morphine/clonidine synergism. Surprisingly, ω-agatoxin IVA reversed the additive morphine/clonidine interaction that occurs in morphine-tolerant mice back to synergism. These results suggest that functional P-type Ca2+channels play an essential role in the antinociceptive synergism between spinal morphine and clonidine.