Capsaicin-Induced Activation of ERK1/2 and Its Involvement in GAP-43 Expression and CGRP Depletion in Organotypically Cultured DRG Neurons

Springer Science and Business Media LLC - Tập 33 - Trang 433-441 - 2013
Yunfeng Li1, Guixiang Liu2, Hao Li3, Youzheng Xu1, Hong Zhang1, Zhen Liu4
1Faculty of Clinical Medicine, Shandong University School of Medicine, Jinan, China
2Department of Histology and Embryology, Binzhou Medical College, Binzhou, China
3Department of Orthopaedics, Shandong University Qilu Hospital, Jinan, China
4Department of Anatomy, Shandong University School of Medicine, Jinan, China

Tóm tắt

Low concentrations of capsaicin (CAP) stimulate and high concentrations of CAP can be toxic to the primary sensory neurons of the dorsal root ganglion (DRG). CAP induces the phosphorylation of extracellular signal-regulated protein kinases 1/2 (ERK1/2) in DRG neurons. The effect of the activation of ERK1/2 by different concentrations of CAP on growth-associated protein 43 (GAP-43) expression and calcitonin gene-related peptide (CGRP) depletion in DRG neurons remains unknown. In the present study, organotypic embryonic 15-day-old rat DRG explants were used to determine the effect of different concentrations of CAP on GAP-43 expression and CGRP depletion. The results showed that, compared to unstimulated control cultures, GAP-43 and pERK1/2 protein levels increased at a low concentration (2 μmol/L) of CAP and decreased at a higher concentration (10 μmol/L). The number of CGRP-immunoreactive (IR) migrating neurons also decreased in CAP-treated cultures. The increase in GAP-43 levels and CGRP depletion could be blocked by the administration of ERK1/2 inhibitor PD98059. The results of the present study imply that CAP at different concentrations has different effects on GAP-43 expression and CGRP depletion. These effects were involved in the activation of ERK1/2 in organotypically cultured DRG neurons stimulated with CAP. These data may provide new insights for further development potential therapeutic applications of CAP with moderate dose on neurogenic inflammation.

Tài liệu tham khảo

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