例如:"lncRNA", "apoptosis", "WRKY"

3'-O-Methylorobol Inhibits the Voltage-Gated Sodium Channel Nav1.7 with Anti-Itch Efficacy in A Histamine-Dependent Itch Mouse Model.

Int J Mol Sci. 2019 Dec 01;20(23)
{{ author.authorName }}{{getOrganisationIndexOf(author)}} {{ author.authorName }}{{getOrganisationIndexOf(author)}}
{{ author.authorName }}{{getOrganisationIndexOf(author)}} {{ author.authorName }}{{getOrganisationIndexOf(author)}}
+ et al

[No authors listed]

Author information
  • {{index+1}} {{ organisation }}

摘要


An itch is a clinical complication that affects millions of patients. However, few treatment options are available. The voltage-gated sodium channel Nav1.7 is predominantly expressed in peripheral sensory neurons and is responsible for the rising phase of action potentials, thereby mediating nociceptive conduction. A gain-of-function mutation of Nav1.7 results in the hyperexcitability of sensory neurons and causes the inherited paroxysmal itch. Conversely, a monoclonal antibody that selectively inhibits Nav1.7 is able to effectively suppress the histamine-dependent itch in mice. Therefore, Nav1.7 inhibitors may possess the potential to relieve the itch. In the present study, using whole-cell voltage-clamp recordings, we demonstrated that 3'-O-methylorobol inhibited Na+ currents in Nav1.7-CHO cells and tetrodotoxin-sensitive Na+ currents in mouse dorsal root ganglion (DRG) neurons with IC50 (half-maximal inhibitory concentration) values of 3.46 and 6.60 μM, respectively. 3'-O-methylorobol also suppressed the tetrodotoxin-resistant Na+ currents in DRG neurons, though with reduced potency (~43% inhibition at 30 µM). 3'-O-methylorobol (10 µM) affected the Nav1.7 by shifting the half-maximal voltage (V1/2) of activation to a depolarizing direction by ~6.76 mV, and it shifted the V1/2 of inactivation to a hyperpolarizing direction by ~16.79 mV. An analysis of 3'-O-methylorobol activity toward an array of itch targets revealed that 3'-O-methylorobol was without effect on histamine H1 receptor, TRPV1, TRPV3, TRPV4, TRPC4 and TRPM8. The intrathecal administration of 3'-O-methylorobol significantly attenuated compound 48/80-induced histamine-dependent spontaneous scratching bouts and the expression level of c-fos in the nuclei of spinal dorsal horn neurons with a comparable efficacy to that of cyproheptadine. Our data illustrated the therapeutic potential for 3'-O-methylorobol for histamine-dependent itching, and the small molecule inhibition of Nav1.7 may represent a useful strategy to develop novel therapeutics for itching.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}

基因功能


  • {{$index+1}}.{{ gene }}

图表


原始数据


 保存测序数据
Sample name
Organism Experiment title Sample type Library instrument Attributes
{{attr}}
{{ dataList.sampleTitle }}
{{ dataList.organism }} {{ dataList.expermentTitle }} {{ dataList.sampleType }} {{ dataList.libraryInstrument }} {{ showAttributeName(index,attr,dataList.attributes) }}

文献解读