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

Yu ping Xu, Jie wen Zhang, Li Li, Zeng you Ye, Yi Zhang, Xiang Gao, Fen Li, Xi sheng Yan, Zhi guo Liu, Lie ju Liu, Xue hong Cao

Research output: Contribution to journalArticle

Abstract

Intracellular second messengers play an important role in capsaicin- and analogous-induced sensitization and desensitization in pain. Fluorescence Ca 2+ imaging, enzyme immunoassay and PKC assay kit were used to determine a novel mechanism of different Ca 2+ 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 1μM, suggesting acute desensitization of TRPV1 receptor activation. Capsaicin-induced intracellular Ca 2+ concentration ([Ca 2+] i) increase depended on extracellular Ca 2+ influx as an initial trigger. The Ca 2+ influx by capsaicin increased PKC activation and SP release. These increases were completely abolished in Ca 2+-free solution, suggesting that the modulation of capsaicin on PKC and SP are Ca 2+-dependent. Interestingly, the maximal cAMP increase by TRPV1 activation was not blocked Ca 2+ removal, suggesting at least in part a Ca 2+-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 Ca 2+-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.

Original languageEnglish (US)
Pages (from-to)30-35
Number of pages6
JournalNeuroscience Letters
Volume517
Issue number1
DOIs
StatePublished - May 23 2012

Keywords

  • Capsaicin
  • Intracellular second messenger
  • Nociceptors
  • Pain
  • TRPV1 receptor

ASJC Scopus subject areas

  • Neuroscience(all)

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    Xu, Y. P., Zhang, J. W., Li, L., Ye, Z. Y., Zhang, Y., Gao, X., Li, F., Yan, X. S., Liu, Z. G., Liu, L. J., & Cao, X. H. (2012). Complex regulation of capsaicin on intracellular second messengers by calcium dependent and independent mechanisms in primary sensory neurons. Neuroscience Letters, 517(1), 30-35. https://doi.org/10.1016/j.neulet.2012.04.011