异丙酚通过激活感觉神经元中的瞬时受体电位锚蛋白 1 型受体亚型恢复瞬时受体电位香草素受体亚型 1 的敏感性。
Propofol restores transient receptor potential vanilloid receptor subtype-1 sensitivity via activation of transient receptor potential ankyrin receptor subtype-1 in sensory neurons.
机构信息
Department of Biological Sciences, Kent State University, Kent, Ohio 44242, USA.
出版信息
Anesthesiology. 2011 May;114(5):1169-79. doi: 10.1097/ALN.0b013e31820dee67.
BACKGROUND
Cross talk between peripheral nociceptors belonging to the transient receptor potential vanilloid receptor subtype-1 (TRPV1) and ankyrin subtype-1 (TRPA1) family has been demonstrated recently. Moreover, the intravenous anesthetic propofol has directly activates TRPA1 receptors and indirectly restores sensitivity of TRPV1 receptors in dorsal root ganglion (DRG) sensory neurons. Our objective was to determine the extent to which TRPA1 activation is involved in mediating the propofol-induced restoration of TRPV1 sensitivity.
METHODS
Mouse DRG neurons were isolated by enzymatic dissociation and grown for 24 h. F-11 cells were transfected with complementary DNA for both TRPV1 and TRPA1 or TRPV1 only. The intracellular Ca concentration was measured in individual cells via fluorescence microscopy. After TRPV1 desensitization with capsaicin (100 nM), cells were treated with propofol (1, 5, and 10 μM) alone or with propofol in the presence of the TRPA1 antagonist, HC-030031 (0.5 μM), or the TRPA1 agonist, allyl isothiocyanate (AITC; 100 μM); capsaicin was then reapplied.
RESULTS
In DRG neurons that contain both TRPV1 and TRPA1, propofol and AITC restored TRPV1 sensitivity. However, in DRG neurons containing only TRPV1 receptors, exposure to propofol or AITC after desensitization did not restore capsaicin-induced TRPV1 sensitivity. Similarly, in F-11 cells transfected with both TRPV1 and TRPA1, propofol and AITC restored TRPV1 sensitivity. However, in F-11 cells transfected with TRPV1 only, neither propofol nor AITC was capable of restoring TRPV1 sensitivity.
CONCLUSIONS
These data demonstrate that propofol restores TRPV1 sensitivity in primary DRG neurons and in cultured F-11 cells transfected with both the TRPV1 and TRPA1 receptors via a TRPA1-dependent process. Propofol's effects on sensory neurons may be clinically important and may contribute to peripheral sensitization to nociceptive stimuli in traumatized tissue.
背景
最近已经证明，属于瞬时受体电位香草酸受体亚型-1（TRPV1）和ankyrin 亚型-1（TRPA1）家族的外周伤害感受器之间存在串扰。此外，静脉麻醉药异丙酚直接激活 TRPA1 受体，并间接恢复背根神经节（DRG）感觉神经元中 TRPV1 受体的敏感性。我们的目的是确定 TRPA1 激活在多大程度上参与介导异丙酚诱导的 TRPV1 敏感性恢复。
方法
通过酶解分离分离小鼠 DRG 神经元，并培养 24 小时。F-11 细胞用 TRPV1 和 TRPA1 的互补 DNA 或仅 TRPV1 转染。通过荧光显微镜测量单个细胞中的细胞内 Ca2+浓度。在用辣椒素（100 nM）使 TRPV1 脱敏后，用异丙酚（1、5 和 10 μM）单独处理细胞，或在用 TRPA1 拮抗剂 HC-030031（0.5 μM）或 TRPA1 激动剂丙烯基异硫氰酸酯（AITC；100 μM）存在的情况下用异丙酚处理细胞；然后重新应用辣椒素。
结果
在含有 TRPV1 和 TRPA1 的 DRG 神经元中，异丙酚和 AITC 恢复了 TRPV1 敏感性。然而，在仅含有 TRPV1 受体的 DRG 神经元中，在脱敏后暴露于异丙酚或 AITC 并不能恢复辣椒素诱导的 TRPV1 敏感性。同样，在转染了 TRPV1 和 TRPA1 的 F-11 细胞中，异丙酚和 AITC 恢复了 TRPV1 敏感性。然而，在仅转染 TRPV1 的 F-11 细胞中，异丙酚和 AITC 均不能恢复 TRPV1 敏感性。
结论
这些数据表明，异丙酚通过依赖于 TRPA1 的过程恢复初级 DRG 神经元和转染 TRPV1 和 TRPA1 受体的培养 F-11 细胞中的 TRPV1 敏感性。异丙酚对感觉神经元的影响在临床上可能很重要，并可能导致创伤组织中对伤害性刺激的外周致敏。
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