Specific involvement of PKC-ε in sensitization of the neuronal response to painful heat
Specific involvement of PKC-ε in sensitization of the neuronal response to painful heat
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DOI：
10.1016/s0896-6273(00)80813-2
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发表时间：
1999-07-01
期刊：
影响因子：
16.2
通讯作者：
McNaughton, PA
中科院分区：
文献类型：
--
作者：
Cesare, P;Dekker, LV;McNaughton, PA
疼痛在感觉中是独特的，因为在暴露于强刺激期间，感知强度增加或敏感化。一种重要的致敏介质是缓激肽（BK），一种由于组织损伤而释放的肽。BK通过激活蛋白激酶C（PKC）的途径增强伤害性神经元中由热激活的膜离子电流。我们发现，五个PKC亚型存在于感觉神经元，但只有PKC-β被易位到细胞膜BK。热反应时，组成性活性PKC-β被纳入伤害性神经元敏化。相反，BK诱导的致敏作用被PKC β的特异性肽抑制剂抑制。我们的结论是，PKC-β是主要负责敏感性的热反应的伤害性感受器缓激肽。
Pain is unique among sensations in that the perceived intensity increases, or sensitizes, during exposure to a strong stimulus. One important mediator of sensitization is bradykinin (BK), a peptide released as a consequence of tissue damage. BK enhances the membrane ionic current activated by heat in nociceptive neurons, using a pathway that involves activation of protein kinase C (PKC). We find that five PKC isoforms are present in sensory neurons but that only PKC-epsilon is translocated to the cell membrane by BK. The heat response is sensitized when constitutively active PKC-epsilon is incorporated into nociceptive neurons. Conversely, BK-induced sensitization is suppressed by a specific peptide inhibitor of PKC-epsilon. We conclude that PKC-epsilon is principally responsible for sensitization of the heat response in nociceptors by bradykinin.