title: Capsaicin-induced activation of ERK1/2 and its involvement in GAP-43 expression and CGRP depletion in organotypically cultured DRG neurons.
abstract: 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.
authors: Faculty of Clinical Medicine, Shandong University School of Medicine, Jinan, 250012, China. yunfengli630@yahoo.com
authors: Yunfeng
authors: Y
authors: Li
authors: Guixiang
authors: G
authors: Liu
authors: Hao
authors: H
authors: Li
authors: Youzheng
authors: Y
authors: Xu
authors: Hong
authors: H
authors: Zhang
authors: Zhen
authors: Z
authors: Liu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D019922:GAP-43 Protein / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats
chemical_list: D019922:GAP-43 Protein; D048049:Extracellular Signal-Regulated MAP Kinases; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin