Activation of the cGMP/Protein Kinase G Pathway by Nitric Oxide Can Decrease TRPV1 Activity in Cultured Rat Dorsal Root Ganglion Neurons.
10.4196/kjpp.2012.16.3.211
- Author:
Yunju JIN
1
;
Jun KIM
;
Jiyeon KWAK
Author Information
1. Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Korea.
- Publication Type:Original Article
- Keywords:
Dorsal root ganglion neuron;
Nitric oxide;
Protein kinase G;
Rat;
TRPV1
- MeSH:
Animals;
Benzoates;
Carbazoles;
Cyclic GMP-Dependent Protein Kinases;
Ganglia, Spinal;
Guanosine;
Guanylate Cyclase;
Hemoglobins;
Humans;
Imidazoles;
Neurons;
Nitric Oxide;
Nitroprusside;
Penicillamine;
Phosphotransferases;
Proteins;
Rats;
Receptors, Cytoplasmic and Nuclear;
Sensory Receptor Cells;
Spinal Nerve Roots;
Tissue Donors
- From:The Korean Journal of Physiology and Pharmacology
2012;16(3):211-217
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 (Icap). NO scavengers, hemoglobin and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO), prevented the inhibitory effect of SNP on Icap. 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 Icap. The PKG inhibitor KT5823 prevented the inhibition of Icap by SNP. These results suggest that NO can downregulate the function of TRPV1 through activation of the cGMP/PKG pathway in peripheral sensory neurons.
