THE ROLE OF CALCIUM IN CAPSAICIN-INDUCED DESENSITIZATION IN RAT CULTURED DORSAL-ROOT GANGLION NEURONS
THE ROLE OF CALCIUM IN CAPSAICIN-INDUCED DESENSITIZATION IN RAT CULTURED DORSAL-ROOT GANGLION NEURONS
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DOI：
10.1016/0306-4522(93)90315-7
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发表时间：
1993-08-01
期刊：
影响因子：
3.3
通讯作者：
BEVAN, S
中科院分区：
文献类型：
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作者：
CHOLEWINSKI, A;BURGESS, GM;BEVAN, S
在培养的单个大鼠背根神经节神经元中测定辣椒素对胞浆Ca ~（2+）浓度（[Ca ~（2+）]i）的影响。辣椒素产生了快速的浓度依赖性（EC 50值为72 nM）增加[Ca 2 +]i，这是完全依赖于Ca 2+进入。暴露的神经元高浓度的辣椒素导致脱敏，但只有在存在外部Ca 2+。提高[Ca 2 +]i与去极化浓度的钾或Ca 2+离子载体离子霉素没有减少响应随后应用辣椒素。辣椒素不诱导脱敏在无钙培养基中，即使[Ca 2 +]，同时提出了与离子霉素加羰基氰间氯苯腙的组合。冈田酸，一种已知的蛋白磷酸酶1和2A的抑制剂，引起了短暂的剂量依赖性（EC 50值，100 nM）的[Ca 2 +]i上升，但没有对辣椒素或辣椒素诱导的脱敏反应的影响。辣椒素拮抗剂capsazepine阻断辣椒素引起的[Ca ~（2+）]i的增加，并阻止脱敏作用的发生。这些结果表明，脱敏作用需要细胞外Ca ~（2+）的存在，不能通过提高[Ca ~（2+）]i的浓度来模拟，可能涉及通过激活的辣椒素操纵的离子通道的Ca ~（2+）内流。
The effects of capsaicin cytosolic Ca2+ concentration ([Ca2+]i) were measured in individual dorsal root ganglion neurons of the rat in culture. Capsaicin produced a rapid concentration-dependent (EC50 value of 72 nM) increase in [Ca2+]i which was entirely dependent on Ca2+ entry. Exposure of the neurons to a high concentration of capsaicin resulted in desensitization, but only in the presence of external Ca2+. Raising [Ca2+]i With a depolarizing concentration of potassium or the Ca2+ ionophore ionomycin did not reduce the response to a subsequent application of capsaicin. Capsaicin did not induce desensitization in Ca2+-free medium even if [Ca2+], was simultaneously raised with a combination of ionomycin plus carbonyl cyanide m-chlorophenyl-hydrazone. Okadaic acid, a known inhibitor of protein phosphatases 1 and 2A, caused a transient dose-dependent (EC50 value, 100 nM) rise in [Ca2+]i, but had no effect on either the responsiveness to capsaicin or capsaicin induced desensitization. The capsaicin antagonist capsazepine blocked the increase in [Ca2+]i evoked by capsaicin and prevented desensitization.These results suggest that desensitization requires the presence of extracellular Ca2+, cannot be mimicked by raising the concentration of [Ca2+]i and may involve Ca2+ entry through activated capsaicin-operated ion channels.