Melittin activates TRPV1 receptors in primary nociceptive sensory neurons via the phospholipase A2 cascade pathways.
Melittin activates TRPV1 receptors in primary nociceptive sensory neurons via the phospholipase A2 cascade pathways.
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蜂毒素通过磷脂酶A2级联途径激活原代伤害感受感官神经元中的TRPV1受体。
DOI：
10.1016/j.bbrc.2011.03.110
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发表时间：
2011-04-29
影响因子：
3.1
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Du YR;Xiao Y;Lu ZM;Ding J;Xie F;Fu H;Wang Y;Strong JA;Zhang JM;Chen J
蜂毒肽（melittin）是蜂毒中的主要肽类，可引起持续性自发痛、原发性热痛和机械性痛敏，并可增强脊髓伤害性感受神经元的兴奋性。然而，蜂毒肽诱导皮肤过敏的潜在机制尚不清楚。应用全细胞膜片钳和钙离子成像技术研究蜂毒素对急性分离的大鼠背根神经节神经元的作用。蜂毒肽诱导60%的小直径（<25 µm）和中等直径（<40 µm）感觉神经元的细胞内钙增加。在电流钳，局部应用蜂毒肽诱发55%的小型和中型神经元测试的持久放电。在电压钳实验中，蜂毒肽以浓度依赖的方式诱发感觉神经元的内向电流。反复应用蜂毒肽引起内向电流的幅度增加。大部分蜂毒素敏感神经元为辣椒素敏感神经元，65%为同种凝集素B4阳性神经元。TRPV 1受体抑制剂Capsazepine可完全阻断蜂毒肽诱导的内向电流和细胞内钙瞬变。信号通路的抑制剂表明，磷脂酶A2，而不是磷脂酶C，参与产生蜂毒素诱导的内向电流。花生四烯酸代谢途径的两个关键成分环氧合酶（考克斯）和脂氧合酶（LOX）的抑制剂，均部分抑制蜂毒肽诱发的内向电流。蛋白激酶A（PKA）的抑制剂，但不是PKC，也取消了蜂毒肽诱导的内向电流。这些结果表明，蜂毒肽可以直接兴奋小型和中型感觉神经元，至少部分通过激活TRPV 1受体通过PLA 2-COX/LOX级联途径。
Previous studies demonstrated that melittin, the main peptide in bee venom, could cause persistent spontaneous pain, primary heat and mechanical hyperalgesia, and enhance the excitability of spinal nociceptive neurons. However, the underlying mechanism of melittin-induced cutaneous hypersensitivity is unknown. Effects of melittin applied topically to acutely dissociated rat dorsal root ganglion neurons were studied using whole-cell patch clamp and calcium imaging techniques. Melittin induced intracellular calcium increases in 60% of small (<25 µm) and medium (<40 µm) diameter sensory neurons. In current clamp, topical application of melittin evoked long-lasting firing in 55% of small and medium-sized neurons tested. In voltage clamp, melittin evoked inward currents in sensory neurons in a concentration-dependent manner. Repeated application of melittin caused increased amplitude of the inward currents. Most melittin-sensitive neurons were capsaicin-sensitive, and 65% were isolectin B4 positive. Capsazepine, the TRPV1 receptor inhibitor, completely abolished the melittin-induced inward currents and intracellular calcium transients. Inhibitors of signaling pathways showed that phospholipaseA2, but not phospholipase C, was involved in producing the melittin-induced inward currents. Inhibitors of cyclooxygenases (COX) and lipoxygenases (LOX), two key components of the arachidonic acid metabolism pathway, each partially suppressed the inward current evoked by melittin. Inhibitors of protein kinase A (PKA), but not of PKC, also abolished the melittin-induced inward currents. These results indicate that melittin can directly excite small and medium-sized sensory neurons at least in part by activating TRPV1 receptors via PLA2-COXs/LOXs cascade pathways.
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DOI：
10.1124/jpet.102.043422
发表时间：
2003-03-01
影响因子：
3.5
作者：
Carr, MJ;Kollarik, M;Undem, BJ
通讯作者：
Undem, BJ
DOI：
10.1016/0005-2760(93)90292-h
发表时间：
1993-02-10
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
STEINER, MR;BOMALASKI, JS;CLARK, MA
通讯作者：
CLARK, MA
影响因子：
2.5
作者：
Yu, YQ;Chen, J
通讯作者：
Chen, J
影响因子：
1.7
作者：
Shin, HK;Kim, JH
通讯作者：
Kim, JH
影响因子：
7.4
作者：
Chen, J;Chen, HS
通讯作者：
Chen, HS