Involvement of voltage-gated sodium channel Na(v)1.8 in the regulation of the release and synthesis of substance P in adult mouse dorsal root ganglion neurons.
This study was conducted to determine whether Na(v)1.8 contributes to the release and/or synthesis of substance P (SP) in adult mice dorsal root ganglion (DRG) neurons. The SP released from cultured DRG neurons of Na(v)1.8 knock-out mice exposed to either capsaicin or KCl was significantly lower than that from wild-type (C57BL/6) mice based on a radioimmunoassay. The SP level of L6 DRG in Na(v)1.8 knock-out mice was also lower than that in wild-type mice. After chronic constriction injury (CCI) of the sciatic nerve, the level of SP decreased in the L6 ipsilateral DRG of wild-type but not Na(v)1.8 knock-out mice. The preprotachykinin-A (PPT-A) mRNAs in L4 - 6 DRGs of Na(v)1.8 knock-out mice also fell to half their normally abundant levels of expression. There were significant increases in Na(v)1.8 expression of the L6 contralateral DRG from wild-type mice and in the percentage of neurons expressing neurokinin-1 receptor in the cytosol of L6 DRGs from wild-type or Na(v)1.8 knock-out mice. These findings suggest that Na(v)1.8 is involved in the regulation of the release and synthesis of SP in the DRG neurons of wild-type mice.
Department of Pharmacology, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, Japan.
He-Bin
HB
Tang
Eri
E
Shiba
Yu-Sang
YS
Li
Norimitsu
N
Morioka
Tai-Xing
TX
Zheng
Nobukuni
N
Ogata
Yoshihiro
Y
Nakata
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020426:Sciatic Neuropathy / Q000378:metabolism; D015222:Sodium Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D015320:Tachykinins / Q000378:metabolism
D062559:NAV1.8 Voltage-Gated Sodium Channel; D011498:Protein Precursors; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; C568317:SCN10A protein, human; C568318:Scn10a protein, mouse; D015222:Sodium Channels; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D011189:Potassium Chloride; D002211:Capsaicin