Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: Induction of TRPV1 desensitization by a biased receptor agonist.

Authors: Elaine E Wang, Hui Li, Shu Wang, Alexander Y Chuang, Huai-Hu Chuang

Journal, date & volume: Channels (Austin), 2011 Nov-Dec , 5, 464-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21829089

Abstract
Selective suppression of hyperactive sensory neurons is an attractive strategy for managing pathological pain. Blocking Na(+) channels to eliminate action potentials and desensitizing transduction channels can both reduce sensory neuron excitability. The novel synthetic vanilloid ligand cap-ET preserves agonist activation of intracellular Ca(2+) signals and large organic cation transport but loses effective electric current induction. Cap-ET can therefore be used to deliver the membrane impermeable Na(+) channel blocker QX-314 to substantially inhibit voltage-activated Na(+) currents. We explored, besides facilitating entry of organic cationic therapeutics, whether cap-ET can also produce receptor desensitization similar to the natural agonist capsaicin. Using the YO-PRO-1 based fluorescent dye uptake assay, we found that cap-ET effectively triggered Ca(2+) dependent desensitization of TRPV1 when the receptor was pre-sensitized with the surrogate oxidative chemical phenylarsine oxide (PAO), suggesting an alternative use of permanently charged cationic capsaicinoids in differential neuronal silencing.