SNX-482
SNX-482 is a toxin from the tarantula Hysterocrates gigas. It acts as a high-affinity blocker of R-type Ca2+ (Cav2.3) channels, but at higher concentrations it can also block other Ca2+ channels and Na+ channels.
Contents
Sources[edit]
SNX-482 is isolated from the venom of the spider Hysterocrates gigas.[1]
Sequence[edit]
GVDKAGCRYMFGGCSVNDDCCPRLGCHSLFSYCAWDLTFSD-OH[1]
Homology[edit]
SNX-482 is homologous to the spider peptides grammatoxin S1A and hanatoxin.[1]
Target[edit]
Cav2.3 (alpha1E, R-type) channel (strong affinity), L-type Ca2+ channel, P/Q type Ca2+ channel, Na+ channel.[1][2][3]
Mode of action[edit]
The compound was initially identified as a selective, voltage-dependent inhibitor of Cav2.3 (a1E, R-type) channels.[1] SNX-482 inhibits native R-type Ca2+ currents at weak nanomolar concentrations in rat neurohypophyseal nerve terminals. However, it does not influence R-type Ca2+ currents at concentrations of 200–500 nM in several types of rat central neurons.[1] Washout could only moderately reverse the R-type Ca2+ channel inhibition after treatment with 200 nM SNX-482. However, application of strong voltage reverses the blocking of R-type Ca2+ channels.[2] SNX-482 needs to interact with a1E domains III and IV to play a role in the significant inhibition of R-type channel gating.[2] Although SNX-482 is generally viewed as a selective inhibitor of Cav2.3 (a1E, R-type) channels, more recently it was shown that it can also inhibit L-type or P/Q type Ca2+ channels and incompletely block Na+ channels.[1][2][3]
Research and therapeutic use[edit]
SNX-482 has been used to elucidate the roles of theaflavin-3-G in transmitter release;[4] furthermore, some research indicated that it inhibits neuronal responses in a neuropathic pain model, so it is possible that SNX-482 can be used to reduce dorsal horn neuronal pain in neuropathic pain therapy.[5]
References[edit]
- ^ a b c d e f g Robert Newcomb, et al., Biochemistry 1998, 37, 15353–15362
- ^ a b c d Emmanuel Bourinet, et al., Biophysical Journal, Volume 81, July 2001 79–88
- ^ a b G Arroyo, et al., Eur J Pharmacol, 2003, 475: 11–8
- ^ Wang, G, et al. (1999) J. Neurosci. 19, 9235
- ^ Elizabeth A, et al., European Journal of Neuroscience, Vol. 25, pp. 3561–3569, 2007