Proton-induced calcitonin gene-related peptide release from rat sciatic nerve axons, in vitro, involving TRPV1
Proton-induced calcitonin gene-related peptide release from rat sciatic nerve axons, in vitro, involving TRPV1
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DOI：
10.1046/j.1460-9568.2003.02811.x
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发表时间：
2003-08-01
影响因子：
3.4
通讯作者：
Sauer, SK
中科院分区：
文献类型：
--
作者：
Fischer, MJM;Reeh, PW;Sauer, SK
我们以前已经表明，大鼠坐骨神经轴突在体外表达辣椒素和热的敏感性，并响应这些刺激与钙依赖性和分级免疫反应性降钙素基因相关肽的释放。刺激囊泡胞吐和香草素受体TRPV1的无髓神经纤维的轴膜的形态学证据也已提交。在这里，我们使用低pH值，高K+或47 degreesC的溶液刺激离体脱鞘坐骨神经测量免疫反应性降钙素基因相关肽的释放。pH 6.1使免疫反应性降钙素基因相关肽释放较基线增加31%，pH 5.2和4.3分别导致对数线性浓度依赖性增加137%和265%。pH 3.4的影响超出线性范围，并且不可逆。在无Ca2+溶液中和在增加的细胞内Ca2+缓冲能力下的刺激强烈降低质子反应。TRPV1拮抗剂辣椒平和钌红显著降低pH 5.2的作用，但不降低pH 6.1的作用。结合刺激的60毫米K+阈下pH 6.3减少了轴突免疫反应性降钙素基因相关肽的反应88%。然而，在pH值为6.3的有害热反应，仅减少了39%，这表明一个隐藏的敏化热低pH值。这是支持的辣椒平的效果，以减少一半的组合响应，表明TRPV1参与敏化，但不是在轴突热反应本身被发现是耐辣椒平。轴突降钙素基因相关肽的释放被认为在神经内膜血流量的活动依赖性自动调节中发挥生理作用。轴突对质子的敏感性和致敏性可能是某些周围神经病变的病理生理机制。
We have shown previously that rat sciatic nerve axons in vitro express sensitivity to capsaicin and heat and responded to these stimuli with a Ca2+-dependent and graded immunoreactive calcitonin gene-related peptide release. Morphological evidence for stimulated vesicular exocytosis and for the vanilloid receptor TRPV1 in the axolemma of the unmyelinated nerve fibres has also been presented. Here we used solutions of low pH, high K+ or 47 degreesC to stimulate isolated desheathed sciatic nerves measuring immunoreactive calcitonin gene-related peptide release. pH 6.1 increased immunoreactive calcitonin gene-related peptide release by 31% over baseline and pH 5.2 and 4.3 caused a log-linear concentration-dependent increase of 137 and 265%, respectively. The effect of pH 3.4 was out of the linear range and not reversible. Stimulation in Ca2+-free solutions and under increased intracellular Ca2+ buffering capacity strongly reduced the proton responses. The TRPV1 antagonists capsazepine and ruthenium red substantially reduced the effects of pH 5.2 but not pH 6.1. Combining a stimulus of 60 mm K+ with the subliminal pH 6.3 reduced the axonal immunoreactive calcitonin gene-related peptide response by 88%. The noxious heat response at pH 6.3, however, was only reduced by 39%, suggesting a hidden sensitization to heat by low pH. This was supported by an effect of capsazepine to reduce the combined response to half, indicative of an involvement of TRPV1 in the sensitization but not in the axonal heat response itself that was found to be resistant to capsazepine. Axonal calcitonin gene-related peptide release is thought to play a physiological role in activity-dependent autoregulation of endoneurial blood flow. Axonal sensitivity to and sensitization by protons may be a pathophysiological mechanism involved in certain peripheral neuropathies.