title: Induction of vanilloid receptor channel activity by protein kinase C.
abstract: Capsaicin or vanilloid receptors (VRs) participate in the sensation of thermal and inflammatory pain. The cloned (VR1) and native VRs are non-selective cation channels directly activated by harmful heat, extracellular protons and vanilloid compounds. 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 tissue and may mediate inflammatory rather than acute thermal pain. 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.
authors.affiliation: Department of Pharmacology, Southern Illinois University School of Medicine, Springfield 62702, USA. lpremkumar@siumed.edu
authors.forename: L S
authors.initials: LS
authors.lastname: Premkumar
authors.forename: G P
authors.initials: GP
authors.lastname: Ahern
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D063388:Endocannabinoids; D004789:Enzyme Activation; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009865:Oocytes; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D053284:Polyunsaturated Alkamides; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011955:Receptors, Drug / Q000096:biosynthesis* / Q000187:drug effects; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D007473:Ion Channels; D053284:Polyunsaturated Alkamides; D011955:Receptors, Drug; D011994:Recombinant Proteins; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D001920:Bradykinin; D002118:Calcium; C078814:anandamide