Taurine replacement attenuates hyperalgesia and abnormal calcium signaling in sensory neurons of STZ-D rats
Taurine replacement attenuates hyperalgesia and abnormal calcium signaling in sensory neurons of STZ-D rats
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DOI：
10.1152/ajpendo.00168.2004
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发表时间：
2005-01-01
影响因子：
5.1
通讯作者：
Stevens, MJ
中科院分区：
文献类型：
--
作者：
Li, F;Obrosova, IG;Stevens, MJ
痛性糖尿病神经病变的病因目前知之甚少，但可能是感觉神经元中继发于钙信号变化的神经元过度兴奋所致。自然产生的氨基酸牛磺酸具有渗透压、抗氧化剂、钙离子调节剂、抑制性神经递质和止痛剂的功能，因此在糖尿病患者中，牛磺酸的缺乏可能使人容易出现神经元过度兴奋和疼痛。本研究报道了牛磺酸对链脲佐菌素糖尿病(STZ-D)大鼠痛觉过敏和感觉神经元钙稳态的影响。非糖尿病大鼠和STZ-D大鼠以添加2%牛磺酸的饲料喂养6~12wk。通过测量对辐射热的后爪退缩潜伏期和对von Frey麻醉仪的退缩阈值来判断热痛觉过敏和机械性痛觉过敏。用Fura 2荧光标记技术研究了L-4-L-6背根神经节神经元的细胞内钙信号转导。用牛磺酸替代糖尿病大鼠，分别减轻了神经传导的缺陷，阻止了机械和热戒断阈值和潜伏期的减少。在糖尿病大鼠的小背根节感觉神经元，细胞内钙离子浓度([Ca~(2+)](I))对KCl的反应恢复缓慢，牛磺酸纠正了73%。在糖尿病大鼠背根神经节感觉神经元上，咖啡因和三磷酸腺苷诱导的[Ca~(2+)](I)瞬变幅度分别降低47%和27%(P<；0.05)，牛磺酸替代后分别校正74%和93%(P<；0.05)。这些数据表明，牛磺酸在神经元钙信号的调节中起重要作用，牛磺酸缺乏可能导致神经过度兴奋和疼痛，从而导致糖尿病。
The etiology of painful diabetic neuropathy is poorly understood, but may result from neuronal hyperexcitability secondary to alterations of Ca2+ signaling in sensory neurons. The naturally occurring amino acid taurine functions as an osmolyte, antioxidant, Ca2+ modulator, inhibitory neurotransmitter, and analgesic such that its depletion in diabetes may predispose one to neuronal hyperexcitability and pain. This study reports the effects of taurine replacement on hyperalgesia and sensory neuron Ca2+ homeostasis in streptozotocin- diabetic (STZ-D) rats. Nondiabetic and STZ-D rats were treated with a 2% taurine-supplemented diet for 6 - 12 wk. Thermal hyperalgesia and mechanical allodynia were determined by measuring hindpaw withdrawal latency to radiant heat and the withdrawal threshold to the von Frey anesthesiometer. Intracellular Ca2+ signaling was explored in neurons from L-4 - L-6 dorsal root ganglia (DRG), using fura 2 fluorescence. Taurine replacement of diabetic rats attenuated deficits of nerve conduction and prevented reductions of mechanical and thermal withdrawal threshold and latency, respectively. In small DRG sensory neurons from diabetic rats, recovery of intracellular Ca2+ concentration ([Ca2+](i)) in response to KCl was slowed and 73% corrected by taurine. The amplitudes of caffeine and ATP-induced [Ca2+] (i) transients were decreased by 47 and 27% ( P < 0.05), respectively, in diabetic rat DRG sensory neurons and corrected by 74 and 93% ( P < 0.05), respectively, by taurine replacement. These data indicate that taurine is important in the regulation of neuronal Ca2+ signaling and that taurine deficiency may predispose one to nerve hyperexcitability and pain, complicating diabetes.