8bwb

Structural highlights

Function

TX90B_PHONI Potent blocker of nociceptor cation channels TRPA1 and high voltage-activated calcium channels (PubMed:12470700, PubMed:15933156, PubMed:27759880). It acts mainly on P/Q-type (Cav2.1/CACNA1A) calcium channels and has a minor effect on L- (Cav1/CACNA1) and N-type (Cav2.2/CACNA1B) calcium channels (PubMed:12470700, PubMed:15933156). Blocks glutamate release in synaptic transmission mediated by calcium channels (PubMed:12470700). The toxin also inhibits the KCl-induced increase of intrasynaptosomal free calcium (PubMed:12470700). It also shows antiproliferative effects on different glioma cell lines (M059J, U-138MG and U-251MG) (PubMed:28202361). In vivo, it shows analgesic effects in rodent models of pain (PubMed:18774645). In addition, it selectively blocks nocifensive responses evoked by reactive TRPA1 channel agonist (PubMed:27759880). Furthermore, it also reduces the TRPA1 channel-dependent hyperalgesia in a model of neuropathic pain induced by the chemotherapeutic agent BTZ (PubMed:27759880). In addition, it causes reduction of tumor area in the mouse glioma model, that is induced by the orthotopic injection of GL261 cells into the brain (PubMed:28202361).^{[1] [2] [3] [4]}

References

1. ↑ Vieira LB, Kushmerick C, Reis HJ, Diniz CR, Cordeiro MN, Prado MA, Kalapothakis E, Romano-Silva MA, Gomez MV. PnTx3-6 a spider neurotoxin inhibits K+-evoked increase in [Ca2+](i) and Ca2+-dependent glutamate release in synaptosomes. Neurochem Int. 2003 Mar;42(4):277-82. PMID:12470700 doi:10.1016/s0197-0186(02)00130-4
2. ↑ Vieira LB, Kushmerick C, Hildebrand ME, Garcia E, Stea A, Cordeiro MN, Richardson M, Gomez MV, Snutch TP. Inhibition of high voltage-activated calcium channels by spider toxin PnTx3-6. J Pharmacol Exp Ther. 2005 Sep;314(3):1370-7. PMID:15933156 doi:10.1124/jpet.105.087023
3. ↑ Souza AH, Ferreira J, Cordeiro MDN, Vieira LB, De Castro CJ, Trevisan G, Reis H, Souza IA, Richardson M, Prado MAM, Prado VF, Gomez MV. Analgesic effect in rodents of native and recombinant Ph alpha 1beta toxin, a high-voltage-activated calcium channel blocker isolated from armed spider venom. Pain. 2008 Nov 15;140(1):115-126. PMID:18774645 doi:10.1016/j.pain.2008.07.014
4. ↑ Nicoletti NF, Erig TC, Zanin RF, Roxo MR, Ferreira NP, Gomez MV, Morrone FB, Campos MM. Pre-clinical evaluation of voltage-gated calcium channel blockers derived from the spider P. nigriventer in glioma progression. Toxicon. 2017 Apr;129:58-67. PMID:28202361 doi:10.1016/j.toxicon.2017.02.001