Complex regulation of capsaicin on intracellular second messengers by calcium dependent and independent mechanisms in primary sensory neurons

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• 作者：Yu-ping Xu^a ; Jie-wen Zhang^a ; Li Li^b ; Zeng-you Ye^b ; Yi Zhang^c ; ^{zy83743670@sina.com} ; Xiang Gao^d ; Fen Li^d ; Xi-sheng Yan^d ; Zhi-guo Liu^e ; Lie-ju Liu^e ; ^{liejuliu@yahoo.cn} ; Xue-hong Cao^b ; ^d ; ^e ; ^{caoxuehong@gmail.com} ; ^{xuehong.cao@mdanderson.org}
• 关键词：Capsaicin ; TRPV1 receptor ; Intracellular second messenger ; Nociceptors ; Pain
• 刊名：Neuroscience Letters
• 出版年：2012
• 期刊代码：52_03043940
• 类别：neu
• 出版时间：23 May, 2012
• 卷：517
• 期：1
• 页码：30-35
• 文件大小：588 K

摘要

Intracellular second messengers play an important role in capsaicin- and analogous-induced sensitization and desensitization in pain. Fluorescence Ca²⁺ imaging, enzyme immunoassay and PKC assay kit were used to determine a novel mechanism of different Ca²⁺ dependency in the signal transduction of capsaicin-induced desensitization. On the average, capsaicin increased cAMP, cGMP concentration and SP release in bell-shaped concentration-dependent manner, with the maximal responses at concentrations around 1 渭M, suggesting acute desensitization of TRPV1 receptor activation. Capsaicin-induced intracellular Ca²⁺ concentration ([Ca²⁺]_i) increase depended on extracellular Ca²⁺ influx as an initial trigger. The Ca²⁺ influx by capsaicin increased PKC activation and SP release. These increases were completely abolished in Ca²⁺-free solution, suggesting that the modulation of capsaicin on PKC and SP are Ca²⁺-dependent. Interestingly, the maximal cAMP increase by TRPV1 activation was not blocked Ca²⁺ removal, suggesting at least in part a Ca²⁺-independent pathway is involved. Further study showed that cAMP increase was totally abolished by G-protein and adenylate cyclase (AC) antagonist, suggesting a G-protein-dependent pathway in cAMP increase. However, SP release was blocked by inhibiting PKC, but not G-protein or AC, suggesting a G-protein independent pathway in SP release. These results suggest that both Ca²⁺-dependent and independent mechanisms are involved in the regulation of capsaicin on second messengers systems, which could be a novel mechanism underlying distinct desensitization of capsaicin and might provide additional opportunities in the development of effective analgesics in pain treatment.