The immunosuppressant FK506 activates capsaicin- and bradykinin-sensitive DRG neurons and cutaneous C-fibers
The immunosuppressant FK506 activates capsaicin- and bradykinin-sensitive DRG neurons and cutaneous C-fibers
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DOI：
10.1016/j.neures.2004.07.005
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发表时间：
2004-11-01
影响因子：
2.9
通讯作者：
Mizumura, K
中科院分区：
文献类型：
--
作者：
Senba, E;Katanosaka, K;Mizumura, K
免疫抑制剂FK506广泛用于治疗特应性皮炎，对神经系统有多种作用。为了阐明FK506局部应用于特应性患者皮肤引起的短暂烧灼感的机制，我们研究了FK506是否直接激活感觉神经元和纤维。对培养的大鼠DRG神经元的Ca 2+成像研究显示，应用FK 506可升高小DRG神经元亚群（3.1%的DRG神经元对高K+溶液有反应）的细胞内Ca 2+水平。当使用DRGs前炎症大鼠时，发生率增加至7.4%。FK506敏感神经元也对随后应用辣椒素（正常大鼠为89.5%，炎症大鼠为100%）和缓激肽（正常大鼠为31.6%，炎症大鼠为80.9%）作出反应。皮肤神经制备中的单纤维记录证实了细胞培养研究的结果，表明FK506的应用增强了对热和缓激肽有反应的单C纤维的神经元放电。这些发现共同表明，在发炎皮肤上应用FK 506可能激活伤害性C纤维，其携带缓激肽受体和TRP家族的辣椒素敏感性热传导器TRPV 1。(C)2004年Elsevier爱尔兰有限公司和日本神经科学学会。All rights reserved.
Immunosuppressant drug FK506, which is widely used for the treatment of atopic dermatitis, has multiple actions on the nervous system. In order to elucidate the mechanisms underlying transient burning sensation elicited by topical application of FK506 to the skin of atopic patients, we investigated if FK506 directly activates sensory neurons and fibers, or not. Ca2+ imaging study on cultured DRG neurons of rats revealed that application of FK506 raised intracellular Ca2+, levels in a subpopulation of small DRG neurons (3.1% of DRG neurons responsive to high K+ solution). When DRGs front inflamed rats were used, the incidence increased to 7.4%. FK506 sensitive neurons also responded to a subsequent application of capsaicin (89.5% in normal, and 100% in inflamed rats) and bradykinin (31.6% in normal, and 80.9% in inflamed rats). Single fiber recordings in the skin-nerve preparation confirmed the results of cell culture study, showing that application of FK506 enhanced neuronal discharges of single C-fibers that are responsive to heat and bradykinin. These findings, taken together, indicate that FK506 application on inflamed skin may activate nociceptive C-fibers, which bear bradykinin receptors and capsaicin-sensitive heat transducer of TRP family, TRPV1. (C) 2004 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.