β2-Microglobulin elicits itch-related responses in mice through the direct activation of primary afferent neurons expressing transient receptor potential vanilloid 1
β2-Microglobulin elicits itch-related responses in mice through the direct activation of primary afferent neurons expressing transient receptor potential vanilloid 1
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DOI：
10.1016/j.ejphar.2017.07.007
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发表时间：
2017-09-05
影响因子：
5
通讯作者：
Uta, Daisuke
中科院分区：
文献类型：
--
作者：
Andoh, Tsugunobu;Maki, Takahito;Uta, Daisuke
尿毒症瘙痒症是血液透析患者的一种令人不快的症状，其发生机制尚不清楚。β 2-微球蛋白（β 2-MG）是众所周知的MHC I类分子，其水平在接受血液透析的患者的血浆中升高。在这项研究中，我们调查了β 2 MG是否是小鼠的促炎原。皮内注射432-MG到吻背诱导抓挠的剂量依赖性方式。皮内注射β 2-MG到脸颊也引起抓挠，但没有擦拭。β 2-MG诱导的抓挠可被阿片受体拮抗剂盐酸纳曲酮抑制。β 2-MG诱导的抓挠不受瘙痒相关受体拮抗剂的抑制（例如，H-1组胺受体（特非那定）、TP血栓烷受体（DCHCH）、BLT 1白三烯B-4受体（CMHVA）和蛋白酶激活受体2（FSLLRY-NH 2））。然而，β 2-MG诱导的抓挠在反复应用辣椒素和选择性瞬时受体电位香草酸1（TRPV 1）拮抗剂（BCTC）脱敏的小鼠中减弱。此外，β 2-MG诱导表达TRPV 1的背根神经节神经元的原代培养物中细胞外信号调节激酶（激活神经元的标志物）的磷酸化。这些结果表明，β 2-MG是一种促过敏原，至少部分是通过表达TRPV 1的初级感觉神经元引起的瘙痒相关反应。
Uremia pruritus is an unpleasant symptom in patients undergoing hemodialysis, and the underlying mechanisms remain unclear. beta 2-Microglobulin (beta 2-MG) is well-known as an MHC class I molecule and its level is increased in the plasma of patients undergoing hemodialysis. In this study, we investigated whether beta 2 MG was a pruritogen in mice. Intradermal injections of 432-MG into the rostral back induced scratching in a dose-dependent manner. Intradermal injection of beta 2-MG into the cheek also elicited scratching, but not wiping. beta 2-MG-induced scratching was inhibited by the-opioid receptor antagonist naltrexone hydrochloride. beta 2-MG induced scratching was not inhibited by antagonists of itch-related receptors (e.g., H-1 histamine receptor (terfenadine), TP thromboxane receptor (DCHCH), BLT1 leukotriene B-4 receptor (CMHVA), and proteinaseactivated receptor 2 (FSLLRY-NH2)). However, beta 2-MG-induced scratching was attenuated in mice desensitized by repeated application of capsaicin and also by a selective transient receptor potential vanilloid 1 (TRPV1) antagonist (BCTC). In addition, beta 2-MG induced phosphorylation of extracellular signal-regulated kinase (a marker of activated neurons) in primary culture of dorsal root ganglion neurons that expressed TRPV1. These results suggest that beta 2-MG is a pruritogen and elicits itch-related responses, at least in part, through TRPV1expressing primary sensory neurons.