Specific involvement of PKC-epsilon in sensitization of the neuronal response to painful heat.
Pain is unique among sensations in that the perceived intensity increases, or sensitizes, during exposure to a strong stimulus. One important mediator of sensitization is bradykinin (BK), a peptide released as a consequence of tissue damage. BK enhances the membrane ionic current activated by heat in nociceptive neurons, using a pathway that involves activation of protein kinase C (PKC). We find that five PKC isoforms are present in sensory neurons but that only PKC-epsilon is translocated to the cell membrane by BK. The heat response is sensitized when constitutively active PKC-epsilon is incorporated into nociceptive neurons. Conversely, BK-induced sensitization is suppressed by a specific peptide inhibitor of PKC-epsilon. We conclude that PKC-epsilon is principally responsible for sensitization of the heat response in nociceptors by bradykinin.
Cesare
P
P
Neuroscience Research Centre, School of Biomedical Sciences, King's College London, Strand, United Kingdom.
Dekker
L V
LV
Sardini
A
A
Parker
P J
PJ
McNaughton
P A
PA
D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005727:Ganglia, Spinal / Q000166:cytology; D006358:Hot Temperature; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051744:Protein Kinase C-epsilon; D051381:Rats; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002273:Carcinogens; D007527:Isoenzymes; C497257:Prkce protein, rat; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D013755:Tetradecanoylphorbol Acetate; D001920:Bradykinin