SNX-482 is a toxin from the tarantula ''

Hysterocrates gigas ''Hysterocrates gigas'' is a member of the tarantula family, Theraphosidae found in Cameroon. It is known as the giant baboon spider, Cameroon red baboon spider, or red baboon tarantula. Description This is a burrowing spider and ranges in ...

''. It acts as a high-affinity blocker of

R-type is a horizontally scrolling shooter arcade video game developed and released by Irem in 1987 and the first game in the ''R-Type'' series. The player controls a star ship, the R-9 "Arrowhead", in its efforts to destroy the Bydo, a powerful ...

Ca²⁺ (Cav2.3) channels, but at higher concentrations it can also block other Ca²⁺ channels and Na⁺ channels.

Sources

SNX-482 is isolated from the

venom Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a st ...

of the spider ''

''.Robert Newcomb, et al., ''Biochemistry'' 1998, 37, 15353–15362

Sequence

GVDKAGCRYMFGGCSVNDDCCPRLGCHSLFSYCAWDLTFSD-OH

Homology

SNX-482 is homologous to the spider peptides grammatoxin S1A and hanatoxin.

Target

Cav2.3 (alpha1E, R-type) channel (strong affinity), L-type Ca²⁺ channel, P/Q type Ca²⁺ channel, Na⁺ channel.Emmanuel Bourinet, et al., ''Biophysical Journal'', Volume 81, July 2001 79–88G Arroyo, et al., ''Eur J Pharmacol'', 2003, 475: 11–8

Mode of action

The compound was initially identified as a selective, voltage-dependent inhibitor of Cav2.3 (a1E, R-type) channels. SNX-482 inhibits native R-type Ca²⁺ currents at weak nanomolar concentrations in rat

neurohypophyseal The posterior pituitary (or neurohypophysis) is the posterior lobe of the pituitary gland which is part of the endocrine system. The posterior pituitary is not glandular as is the anterior pituitary. Instead, it is largely a collection of axonal ...

nerve terminals. However, it does not influence R-type Ca²⁺ currents at concentrations of 200–500 nM in several types of rat central neurons. 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. SNX-482 needs to interact with a1E domains III and IV to play a role in the significant inhibition of R-type channel gating. 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.

Research and therapeutic use

SNX-482 has been used to elucidate the roles of theaflavin-3-G in

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release. Furthermore, some research has indicated that it inhibits neuronal responses in a

neuropathic pain Neuropathic pain is pain caused by damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous ...

model, so it is possible that SNX-482 can be used to reduce dorsal horn neuronal pain in

therapy A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health problem, usually following a medical diagnosis. As a rule, each therapy has indications and contraindications. There are many differe ...

.Elizabeth A, et al., ''European Journal of Neuroscience'', Vol. 25, pp. 3561–3569, 2007

References

{{Reflist Ion channel toxins Neurotoxins