Activation of the cGMP/Protein Kinase G Pathway by Nitric Oxide Can Decrease TRPV1 Activity in Cultured Rat Dorsal Root Ganglion Neurons

Activation of the cGMP/Protein Kinase G Pathway by Nitric Oxide Can Decrease TRPV1 Activity in Cultured Rat Dorsal Root Ganglion Neurons

Recent studies have demonstrated that nitric oxide (NO) activates transient receptor potential vanilloid subtype 1 (TRPV1) via S-nitrosylation of the channel protein. NO also modulates various cellular functions via activation of the soluble guanylyl cyclase (sGC)/protein kinase G (PKG) pathway and the direct modification of proteins. Thus, in the present study, we investigated whether NO could indirectly modulate the activity of TRPV1 via a cGMP/PKG-dependent pathway in cultured rat dorsal root ganglion (DRG) neurons. NO donors, sodium nitroprusside (SNP) and S-nitro-N-acetylpenicillamine (SNAP), decreased capsaicin-evoked currents (I_cap). NO scavengers, hemoglobin and 2-(4-carboxyphenyl)- 4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO), prevented the inhibitory effect of SNP on I_cap. Membrane-permeable cGMP analogs, 8-bromoguanosine 3 , 5 -cyclic monophosphate (8bromo-cGMP) and 8-(4chlorophenylthio)-guanosine 3 ,5 -cyclic monophosphate (8-pCPT-cGMP), and the guanylyl cyclase stimulator YC-1 mimicked the effect of SNP on I_cap. The PKG inhibitor KT5823 prevented the inhibition of I_cap by SNP. These results suggest that NO can downregulate the function of TRPV1 through activation of the cGMP/PKG pathway in peripheral sensory neurons.