The Journal of Neuroscience, June 29, 2005, ():
Epac Mediates a cAMP-to-PKC Signaling in Inflammatory Pain: An Isolectin B4(+) Neuron-Specific Mechanism
J. Neurosci. Hucho et al.
25: 6119
Supplemental data
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Supplemental Figure: β2-AR agonists signal through Epac, PI-PLC and PLD to PKCε, resulting in mechanical hyperalgesia
Schematic of proposed second messenger signaling cascade for β2-AR agonist-induced mechanical hyperalgesia includes G-protein αs leading to activation of AC and Epac in the peripheral terminal of the primary afferent nociceptor. PKA is not involved in β2-AR-induced/PKCε-mediated sensitization. Epac leads to the activation of PI-PLC and PLD, the activity of both of which is necessary for the translocation of PKCε in vitro and the onset of Epac/PKCε-mediated hyperalgesia in vivo. As shown earlier, PKCε activation leads to an increase in the TTX-R sodium current (Khasar et al., 1999b), which has a central role in hyperalgesia. Activators/inhibitors used are indicated at their respective level of action on the right of the scheme.
