Protein kinase C epsilon contributes to basal and sensitizing responses of TRPV1 to capsaicin in rat dorsal root ganglion neurons.
Phosphorylation of the vanilloid receptor (TRPV1) by protein kinase C epsilon (PKCepsilon) plays an important role in the development of chronic pain. Here, we employ a highly defective herpes simplex virus vector (vHDNP) that expresses dominant negative PKCepsilon (DNPKCepsilon) as a strategy to demonstrate that PKCepsilon is essential for: (i) maintenance of basal phosphorylation and normal TRPV1 responses to capsaicin (CAPS), a TRPV1 agonist and (ii) enhancement of TRPV1 responses by phorbol esters. Phorbol esters induced translocation of endogenous PKCepsilon to the plasma membrane and thereby enhanced CAPS currents. These results were extended to an in-vivo pain model in which vHDNP delivery to dorsal root ganglion neurons caused analgesia in CAPS-treated, acutely inflamed rat hind paws. These findings support the conclusion that in addition to receptor sensitization, PKCepsilon is essential for normal TRPV1 responses in vitro and in vivo.
Srinivasan
Rahul
R
Department of Microbiology and Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Wolfe
Darren
D
Goss
James
J
Watkins
Simon
S
de Groat
William C
WC
Sculptoreanu
Adrian
A
Glorioso
Joseph C
JC
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D018689:Sensory System Agents / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000819:agonists / Q000378:metabolism*
D002273:Carcinogens; D010703:Phorbol Esters; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D051744:Protein Kinase C-epsilon; D002211:Capsaicin