Interaction between protein kinase D1 and transient receptor potential V1 in primary sensory neurons is involved in heat hypersensitivity

Pain. 2008 Jul 31;137(3):574-88. doi: 10.1016/j.pain.2007.10.025. Epub 2007 Dec 3.

Abstract

In previous studies we demonstrated that protein kinase D1 (PKD1/PKCmu) could directly phosphorylate the transient receptor potential V1 (TRPV1) at its N-terminal region and enhance the function of TRPV1 in CHO cells stably transfected with TRPV1. In the current study we assessed the involvement of PKD1 in pain modulation and explored the possible interaction between PKD1 and TRPV1 in rat inflammatory heat hypersensitivity. PKD1 was translocated to cytoplasmic membrane fraction and was trans-phosphorylated only in membrane fraction but not in cytoplasmic fraction of dorsal root ganglia (DRG) at 2 and 6h after Complete Freund's Adjuvant (CFA) treatment. Pre i.t. injection of PKD1 antisense for 4 d or post-i.t. injection for 4 d both alleviated CFA-induced thermal hypersensitivity. Likewise, overexpression of PKD1 in DRG significantly enhanced, while dominant negative PKD1 (DN-PKD1) partly attenuated, heat hypersensitivity. Both PKD1 and TRPV1 were translocated to the cytoplasmic membrane in DRG 6 h after CFA treatment and, at that time, PKD1 interacted with TRPV1 by co-immunoprecipitation in DRG. Electrophysiological measurements indicated that DRG with overexpression of PKD1 were more sensitive to low dose capsaicin than those expressing DN-PKD1. The average magnitude of the peak inward current evoked by capsaicin was greater in the DRG overexpressing PKD1 than in those expressing DN-PKD1. Furthermore, overexpressed PKD1 could up regulate, whereas PKD1 antisense could knock down TRPV1 content in DRG through posttranscriptional regulation manner. We concluded that PKD1 in DRG, through interaction with TRPV1, is involved in developing and maintaining inflammatory heat hypersensitivity.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Ganglia, Spinal / physiopathology*
  • Hot Temperature
  • Hyperalgesia / physiopathology*
  • Male
  • Posterior Horn Cells / physiopathology*
  • Protein Kinase C
  • Protein Kinases / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • TRPV Cation Channels / metabolism*

Substances

  • TRPV Cation Channels
  • Trpv1 protein, rat
  • Protein Kinases
  • protein kinase D
  • Protein Kinase C