RhTx
RhTx is a small peptide toxin from Scolopendra subspinipes mutilans, also called the Chinese red-headed centipede. RhTx binds to the outer pore region of the temperature regulated TRPV1 ion channel, preferably in activated state, causing a downwards shift in the activation threshold temperature, which leads to the immediate onset of heat pain.[1]
Sources
RhTx is a component of the venom of the S. subspinipes mutilans, also called the Chinese red-headed centipede.[1]
Chemistry
RhTx is a small
Target
RhTx binds to the outer pore region of the polymodal TRPV1 ion channel. The toxin preferably binds to TRPV1 in the activated state of the channel. RhTx has a high affinity for the TRPV1 ion channel, which results in very rapid binding and slow unbinding. The TRPV1 channel is a non-selective cation channel, with a high permeability to Ca2+.[2] TRPV1 is mainly expressed in sensory neurons and can be activated by different stimuli, including high temperatures (heat), acids, pollutants with negative electric charge and endogenous metabolites such as anandamide.[3] The channel is also targeted by the active component of chilli peppers capsaicin, and the spider toxins Vanillotoxin and DkTx.[3][4][5]
Mode of action
After binding to the outer pore region of the TRPV1, RhTx can interact with both the turret and the pore helix through electrostatic and
Toxicity
In mice, injections of RhTx induced pain behavior, which was distinct from pain behavior mediated by inflammation, but similar to the behavior elicited by capsaicin injection. Injections in mice also caused a rapid drop of core body temperature at normal conditions, by less than 1 degree Celsius. The EC50 in mice is estimated to be 500 nM.[1] While the effect of isolated RhTx administration is not known in humans, bites of the
References
- ^ a b c d e f
Yang, S., Yang, F., Wei, N., Hong, J., Li, B., Luo, L., ... & Lai, R. (2015). A pain-inducing centipede toxin targets the heat activation machinery of nociceptor TRPV1. Nature Communications, 6. PMID 26420335
- PMID 11283319
- ^ a b Cortright, D. N. and Szallasi, A. (2004). Biochemical pharmacology of the vanilloid receptor TRPV1. European Journal of Biochemistry, 271: 1814–1819.
PMID 15128291
- PMID 17093448
- PMID 20510930
- ^ PMID 25478303