Induction of vanilloid receptor channel activity by protein kinase C

Capsaicin or vanilloid receptors (VRs) participate in the sensation of ther mal and inflammatory pain(1-3). The cloned (VR1) and native VRs are non-sel ective cation channels directly activated by harmful heat, extracellular pr otons and vanilloid compounds(4-8). However, considerable attention has bee n focused on identifying other signalling pathways in VR activation; it is known that VR1 is also expressed in non-sensory tissue(1,9) and may mediate inflammatory rather than acute thermal pain(3). Here we show that activati on of protein kinase C (PKC) induces VR1 channel activity at room temperatu re in the absence of any other agonist. We also observed this effect in nat ive VRs from sensory neurons, and phorbol esters induced a vanilloid-sensit ive Ca2+ rise in these cells. Moreover, the pro-inflammatory peptide, brady kinin, 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.