Thermal nociception and TRPV1 function are attenuated in mice lacking the nucleotide receptor P2Y2
Thermal nociception and TRPV1 function are attenuated in mice lacking the nucleotide receptor P2Y2
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DOI：
10.1016/j.pain.2008.01.026
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发表时间：
2008-09-15
期刊：
影响因子：
7.4
通讯作者：
Molliver, Derek C.
中科院分区：
文献类型：
--
作者：
Malin, Sacha A.;Davis, Brian M.;Molliver, Derek C.
最近的研究表明，ATP和UTP作用于G蛋白偶联（P2Y）核苷酸受体，以兴奋伤害性感觉神经元;核苷酸还通过亲伤害性辣椒素受体TRPV1增强信号传导。我们在此证明P2Y（2）是躯体感觉神经元中的主要UTP受体：P2Y（2）在背根神经节中高度表达，并且P2Y（2）（-/-）小鼠也缺乏对疼痛性热的检测：基线热反应潜伏期增加，并且突变小鼠在对炎性损伤（将完全弗氏佐剂注射到后爪中）的反应中未能发展热超敏反应。P2Y（2）是唯一的Gq-偶联P2Y受体，显示DRG mRNA水平在炎症反应中增加。令人惊讶的是，TRPV1的功能也减弱P2Y（2）（-/-）小鼠，通过辣椒素反应的频率和幅度在体外和辣椒素给药在体内的行为反应进行测量。然而，TRPV1 mRNA水平和免疫反应性并没有降低，并且通过缓激肽预处理可以在很大程度上恢复P2Y（2）（-/-）小鼠对辣椒素的行为敏感性，这表明TRPV1的正常功能需要G蛋白偶联受体的持续调节。这些结果表明，通过P2Y（2）的核苷酸信号传导在热伤害感受中起关键作用。(C)2008年国际疼痛研究协会。Elsevier B.V.出版，保留所有权利。
Recent studies indicate that ATP and UTP act at G protein-coupled (P2Y) nucleotide receptors to excite nociceptive sensory neurons; nucleotides also potentiate signaling through the pro-nociceptive capsaicin receptor, TRPV1. We demonstrate here that P2Y(2) is the principal UTP receptor in somatosensory neurons: P2Y(2) is highly expressed in dorsal root ganglia and P2Y(2)(-/-) mice were also deficient in the detection of painful heat: baseline thermal response latencies were increased and mutant mice failed to develop thermal hypersensitivity in response to inflammatory injury (injection of complete Freund's adjuvant into the hindpaw). P2Y(2) was the only Gq-coupled P2Y receptor examined that showed an increase in DRG mRNA levels in response to inflammation. Surprisingly, TRPV1 function was also attenuated in P2Y(2)(-/-) mice, as measured by the frequency and magnitude of capsaicin responses in vitro and behavioral responses to capsaicin administration in vivo. However, TRPV1 mRNA levels and immunoreactivity were not reduced, and behavioral sensitivity to capsaicin could be largely restored in P2Y(2)(-/-) mice by pretreatment with bradykinin, suggesting that normal function of TRPV1 requires ongoing modulation by G protein-coupled receptors. These results indicate that nucleotide signaling through P2Y(2) plays a key role in thermal nociception. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.