Ca2+ waves in keratinocytes are transmitted to sensory neurons:: the involvement of extracellular ATP and P2Y2 receptor activation
Ca2+ waves in keratinocytes are transmitted to sensory neurons:: the involvement of extracellular ATP and P2Y2 receptor activation
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DOI：
10.1042/bj20031089
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发表时间：
2004-06-01
影响因子：
4.1
通讯作者：
Inoue, K
中科院分区：
文献类型：
--
作者：
Koizumi, S;Fujishita, K;Inoue, K
ATP在多种细胞中充当细胞间信使。在本研究中，我们的特点是传播的Ca2+波介导的细胞外ATP在培养的NHEKs（正常人表皮角质形成细胞），与小鼠DRG（背根神经节）神经元共培养。药理学特征表明，NHEK表达功能性代谢型P2Y（2）受体。当用玻璃移液管轻轻刺激细胞时，观察到[Ca 2 +]（i）（细胞内Ca 2+浓度）增加，随后以细胞外ATP依赖性方式诱导邻近细胞中传播的Ca 2+波。使用ATP成像技术，证实了ATP在NHEK中的释放和扩散。已知DRG神经元终止于角质形成细胞的基底层。在NHEK和DRG神经元的共培养中，机械刺激诱发的NHEK中的Ca 2+波引起邻近DRG神经元中的[Ca 2 +]（i）增加，这也依赖于细胞外ATP和P2Y（2）受体的激活。总之，细胞外ATP是在NHEK中形成细胞间Ca2+波的主要信使。此外，NHEK中的Ca 2+波可引起DRG神经元中[Ca 2 +]（i）的增加，表明皮肤和感觉神经元之间由细胞外ATP介导的动态串扰。
ATP acts as an intercellular messenger in a variety of cells. In the present study, we have characterized the propagation of Ca2+ waves mediated by extracellular ATP in cultured NHEKs (normal human epidermal keratinocytes) that were co-cultured with mouse DRG (dorsal root ganglion) neurons. Pharmacological characterization showed that NHEKs express functional metabotropic P2Y(2) receptors. When a cell was gently stimulated with a glass pipette, an increase in [Ca2+](i) (intracellular Ca2+ concentration) was observed, followed by the induction of propagating Ca2+ waves in neighbouring cells in an extracellular ATP-dependent manner. Using an ATP-imaging technique, the release and diffusion of ATP in NHEKs were confirmed. DRG neurons are known to terminate in the basal layer of keratinocytes. In a coculture of NHEKs and DRG neurons, mechanical-stimulation-evoked Ca2+ waves in NHEKs caused an increase in [Ca2+](i) in the adjacent DRG neurons, which was also dependent on extracellular ATP and the activation of P2Y(2) receptors. Taken together, extracellular ATP is a dominant messenger that forms intercellular Ca2+ waves in NHEKs. In addition, Ca2+ waves in NHEKs could cause an increase in [Ca2+](i) in DRG neurons, suggesting a dynamic cross-talk between skin and sensory neurons mediated by extracellular ATP.