Effects of local anesthetics on opioid inhibition of calcium current in rat dorsal root ganglion neurons.
Effects of local anesthetics on opioid inhibition of calcium current in rat dorsal root ganglion neurons.
复制标题
局麻药对阿片类药物抑制大鼠背根神经节神经元钙电流的影响。
DOI：
10.1016/j.neulet.2007.03.041
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发表时间：
2007
影响因子：
2.5
通讯作者：
McDowell,ThomasS
中科院分区：
文献类型：
--
作者：
Komai,Hirochika;McDowell,ThomasS
通常使用局部麻醉剂和阿片类药物的混合物来提供神经轴向镇痛。这种药物的组合提供了更好的疼痛缓解，并且通常比单独使用任何一种药物时副作用更少。局部麻醉剂已被证明可以改变其他G蛋白偶联受体的信号传导，但对阿片受体信号传导的影响知之甚少。由于阿片类药物产生镇痛至少部分通过抑制突触前钙通道，我们已经评估了丁卡因和布比卡因对阿片类药物介导的抑制背根神经节神经元钙通道的影响。μ-阿片特异性激动剂DAMGO（1μM）在不存在和存在丁卡因（50或100μM）的情况下均抑制Ca通道。然而，在存在两种浓度的丁卡因的情况下，DAMGO抑制的程度小于在不存在丁卡因的情况下观察到的程度。DAMGO抑制从对照的39.2±24.4%降低到50μM丁卡因的34.2±24.4%（n=16; p<0.05），从对照的40.5±19.6%降低到100μM丁卡因的34.6±20.5%（n=10; p<0.05）。布比卡因也有类似的结果。丁卡因还降低了DAMGO或非水解GTP类似物（GTPγS）激活G蛋白时Ca通道电流的电压依赖性易化作用，表明丁卡因减弱了G蛋白βγ亚基与Ca通道之间的相互作用。总体而言，这些结果表明，局部麻醉剂通过干扰阿片受体和Ca通道之间的GTP介导的信号转导来降低阿片对Ca通道活性的抑制。
Neuraxial analgesia is often provided using a mixture of local anesthetics and opioids. This combination of agents provides better pain relief and is generally associated with fewer side effects than when either drug is given alone. Local anesthetics have been shown to alter signaling of other G protein-coupled receptors, but little is known about their effect on opioid receptor signaling. Because opioids produce analgesia at least in part by inhibiting presynaptic Ca channels, we have evaluated the effects of tetracaine and bupivacaine on opioid-mediated inhibition of Ca channels in dorsal root ganglion neurons. The μ-opioid specific agonist DAMGO (1μM) inhibited Ca channels in both the absence and presence of tetracaine (50 or 100μM). However, the extent of DAMGO inhibition in the presence of both concentrations of tetracaine was less than that observed in the absence of tetracaine. DAMGO inhibition decreased from 39.2±24.4% in control to 34.2±24.4% with 50μM tetracaine (n=16; p<0.05), and from 40.5±19.6% in control to 34.6±20.5% with 100μM tetracaine (n=10; p<0.05). Similar results were seen with bupivacaine. Tetracaine also decreased the voltage-dependent facilitation of Ca channel currents when G proteins were activated by either DAMGO or the non-hydrolyzable GTP analogue (GTPγS), suggesting that tetracaine weakens the interaction between G protein βγ subunits and the Ca channel. Overall, these results suggest that local anesthetics decrease opioid inhibition of Ca channel activity by interfering with the GTP-mediated signal transduction between opioid receptors and Ca channels.