Increases in transient receptor potential vanilloid-1 mRNA and protein in primary afferent neurons stimulated by protein kinase C and their possible role in neurogenic inflammation.
A recent study by our group demonstrates pharmacologically that the transient receptor potential vanilloid-1 (TRPV(1)) is activated by intradermal injection of capsaicin to initiate neurogenic inflammation by the release of neuropeptides in the periphery. In this study, expression of TRPV(1), phosphorylated protein kinase C (p-PKC), and calcitonin gene-related peptide (CGRP) in dorsal root ganglion (DRG) neurons was visualized by using immunofluorescence, real-time PCR, and Western blots to examine whether increases in TRPV(1) mRNA and protein levels evoked by capsaicin injection are subject to modulation by the activation of PKC and to analyze the role of this process in the pathogenesis of neurogenic inflammation. Capsaicin injection into the hindpaw skin of anesthetized rats evoked increases in the expression of TRPV(1), CGRP and p-PKC in mRNA and/or protein levels and in the number of single labeled TRPV(1), p-PKC, and CGRP neurons in ipsilateral L4-5 DRGs. Coexpressions of TRPV(1) with p-PKC and/or CGRP in DRG neurons were also significantly increased after CAP injection. These evoked expressions at both molecular and cellular levels were significantly inhibited after TRPV(1) receptors were blocked by 5'-iodoresiniferatoxin (5 microg) or PKC was inhibited by chelerythrine chloride (5 microg). Taken together, these results provide evidence that up-regulation of TRPV(1) mRNA and protein levels under inflammatory conditions evoked by capsaicin injection is subject to modulation by the PKC cascade in which increased CGRP level in DRG neurons may be related to the initiation of neurogenic inflammation. Thus, up-regulation of TRPV(1) receptors in DRG neurons seems critical for initiating acute neurogenic inflammation.
Xu
Xijin
X
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas 77555-1069, USA.
Wang
Peng
P
Zou
Xiaoju
X
Li
Dingge
D
Fang
Li
L
Lin
Qing
Q