Sugiura Takeshi, Tominaga Makoto, Katsuya Hirotada, Mizumura Kazue
Department of Anesthesiology and Resuscitology, Nagoya City University Medical School, Nagoya 467-0001, Japan.
J Neurophysiol. 2002 Jul;88(1):544-8. doi: 10.1152/jn.2002.88.1.544.
Bradykinin (BK) is an inflammatory mediator that plays a pivotal role in pain and hyperalgesia to heat in inflamed tissues by exciting nociceptors and sensitizing them to heat through activation of protein kinase C (PKC). It has been suggested that the capsaicin receptor (VR1), a nociceptor-specific cation channel sensitive to noxious heat, protons, and capsaicin, is a channel that is modified by BK in these effects. In this study, we examined how BK modulates the activity of VR1. We measured VR1 currents using the patch-clamp technique in human embryonic kidney-derived (HEK293) cells expressing VR1 and B2 BK receptor. We found that BK lowered the threshold temperature for activation of VR1 currents in HEK cells down to well below the physiological body temperature in a concentration-dependent manner through PKC activation. We also demonstrated that in capsaicin-sensitive dorsal root ganglion (DRG) neurons the activation threshold of heat-induced current, which is considered to be VR-1 mediated, was lowered by BK and that this effect was also mediated by PKC. These data further support the supposition that modulation of VR1 is a mechanism for the BK-induced excitation of nociceptors and their sensitization to heat.
缓激肽（BK）是一种炎症介质，通过激活伤害感受器并通过蛋白激酶C（PKC）的激活使其对热敏感，在炎症组织的疼痛和热痛觉过敏中起关键作用。有人提出，辣椒素受体（VR1）是一种对有害热、质子和辣椒素敏感的伤害感受器特异性阳离子通道，是BK在这些效应中修饰的通道。在本研究中，我们研究了BK如何调节VR1的活性。我们使用膜片钳技术在表达VR1和B2 BK受体的人胚胎肾来源（HEK293）细胞中测量VR1电流。我们发现，BK通过PKC激活以浓度依赖的方式将HEK细胞中VR1电流的激活阈值降低到远低于生理体温的水平。我们还证明，在对辣椒素敏感的背根神经节（DRG）神经元中，被认为是由VR-1介导的热诱导电流的激活阈值被BK降低，并且这种效应也是由PKC介导的。这些数据进一步支持了VR1的调节是BK诱导伤害感受器兴奋及其对热敏感化的机制这一假设。
