Capsaicin or vanilloid receptors (VRs) participate in the sensation of thermal and inflammatory pain1,2,3. The cloned (VR1) and native VRs are non-selective cation channels directly activated by harmful heat, extracellular protons and vanilloid compounds4,5,6,7,8. However, considerable attention has been focused on identifying other signalling pathways in VR activation; it is known that VR1 is also expressed in non-sensory tissue1,9 and may mediate inflammatory rather than acute thermal pain3. Here we show that activation of protein kinase C (PKC) induces VR1 channel activity at room temperature in the absence of any other agonist. We also observed this effect in native VRs from sensory neurons, and phorbol esters induced a vanilloid-sensitive Ca2+ rise in these cells. Moreover, the pro-inflammatory peptide, bradykinin, and the putative endogenous ligand, anandamide, respectively induced and enhanced VR activity, in a PKC-dependent manner. These results suggest that PKC may link a range of stimuli to the activation of VRs.
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We thank D. Hallam for assistance with the culture of DRG neurons, and M. Caterina and D. Julius for the gift of VR1. This work was supported by the NSF.
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Premkumar, L., Ahern, G. Induction of vanilloid receptor channel activity by protein kinase C. Nature 408, 985–990 (2000). https://doi.org/10.1038/35050121
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