220 € – 1309 €
Huwentoxin-I (HwTx-I) is a neurotoxin that was originally isolated from the venom of the Chinese bird spider Ornithoctonus huwena. Huwentoxin-I is known to be an inhibitor of tetrodotoxin-sensitive voltage-gated sodium channels (TTX-S) (IC50 ~ 50 nM) and N-type voltage-sensitive calcium channels (IC50 ~ 100 nM) in mammalian DRG, hippocampus and insect’s DUM neurons. It has only a very weak effect on L-type calcium channels, no effect on TTX-R channels and has virtually no effect on muscle sodium channels. The selectivity of Huwentoxin-I for calcium channels appears to be higher than ω-conotoxin MVIIA and equivalent to ω-conotoxin GVIA. Huwentoxin-I demonstrated an antinociceptive effect in the rat model of the formalin test when administrated intrathecally (ED50 ~ 0.28 µg/kg), without side effects of the ones led by ω-conotoxin MVIIA.
AA sequence: Ala-Cys2-Lys-Gly-Val-Phe-Asp-Ala-Cys9-Thr-Pro-Gly-Lys-Asn-Glu-Cys16-Cys17-Pro-Asn-Arg-Val-Cys22-Ser-Asp-Lys-His-Lys-Trp-Cys26-Lys-Trp-Lys-Leu-OH
Disulfide bonds: Cys2-Cys17, Cys9-Cys22 and Cys16-Cys29
Length (aa): 33
Formula: C161H246N48O44S6
Molecular Weight: 3751.77 Da
Appearance: White lyophilized solid
Solubility: water and saline buffer
CAS number:
Source: Synthetic
Purity rate: > 97 %
| ProTx-I | ProTx-II | ProTx-II-Biotin |
| ω-Conotoxin-MVIIA | Huwentoxin-IV | Hainantoxin-III |
| Hainantoxin-IV | GsAF-2 | GsAF-1 |
| ω-Conotoxin-GVIA |
Huwentoxin-I (HWTX-I) is a 33-residue peptide isolated from the venom of Ornithoctonus huwena and could inhibit TTX-sensitive voltage-gated sodium channels and N-type calcium channels in mammalian dorsal root ganglion (DRG) neurons. However, the effects of HWTX-I on mammalian central neuronal and insect sodium channel subtypes remain unknown. In this study, we found that HWTX-I potently inhibited sodium channels in rat hippocampal and cockroach dorsal unpaired median (DUM) neurons with the IC(50) values of 66.1±5.2 and 4.80±0.58nM, respectively. Taken together with our previous work on DRG neurons (IC(50)≈55nM), the order of sodium channel sensitivity to HWTX-I inhibition was insect central DUM≫mammalian peripheral>mammalian central neurons. HWTX-I exhibited no effect on the steady-state activation and inactivation of sodium channels in rat hippocampal and cockroach DUM neurons.
Wang M, et al. (2012) The effects of huwentoxin-I on the voltage-gated sodium channels of rat hippocampal and cockroach dorsal unpaired median neurons. Peptides. PMID: 22094230
Rheumatoid arthritis (RA) is one of the inflammatory kinds of arthritis in the clinical situation, and cytosolic Ca2+ overload has been proposed as one of the primary factors for many inflammatory cells activation, which lead to relative enzymes and inflammatory factors release. It is therefore accepted that Ca2+ channel blockers can protect joint injury from inflammation. In the present study we investigated the possible molecular mechanism of the antinociceptive efficacy of HWTX-I, a spider peptide toxin blocking Ca2+ channels, on the rat rheumatoid arthritis model. Our study demonstrates that HWTX-I can relieve pain in the inflammatory joints and eliminate arthrocele to some degree. Moreover, HWTX-I can also decrease the concentration of tumour necrosis factor α (TNF-α) and increase the concentration of interleukin 4(IL-4) and interleukin 10(IL-10) in rat’s serum. HWTX-I can also decrease the mRNA expression level of related factors of TNF-α, interleukin 1β (IL-1β) and interleukin 6(IL-6) in inflammatory pathways in rheumatoid arthritis. Therefore, the present results show that the epidural administration of HWTX-I is effective in antinociception in the rat model of rheumatoid arthritis, which may act through its inhibition on certain inflammatory pathways.
Wen Tao Z, et al. (2011) The antinociceptive efficacy of HWTX-I epidurally administered in rheumatoid arthritis rats. Int J Sports Med. PMID: 22052031
In this paper, we investigated the action of huwentoxin-I (HWTX-I) purified from the venom of the Chinese bird spider Ornithoctonus huwena on Ca(2+), Na(+) channels of adult rat dorsal root ganglion (DRG) neurons. The results showed that huwentoxin-I could reduce the peak currents of N-type Ca(2+) channels (IC(50) approximately 100 nM) and TTX-S Na(+) channels (IC(50) approximately 55 nM), whereas no effect was detected on TTX-R Na(+) channels. The comparative studies indicated that the selectivity of HWTX-I on Ca(2+) channels was higher that of MVIIA and approximately the same as that of GVIA. HWTX-I is the first discovered toxin with the cross channel activities from the spider O. huwena venom similar to micro O-conotoxins MrVIA and MrVIB.
Wang M, et al. (2007) The cross channel activities of spider neurotoxin huwentoxin-I on rat dorsal root ganglion neurons. Biochem Biophys Res Commun. PMID: 17451655
Neuronal injury is the most important reason for various brain injuries. Cytosolic Ca(2+) overloading has been proposed as one of the main cellular processes leading to neuronal death during cerebral ischemia. It is well accepted that Ca(2+) channel blockers can protect cerebral neurons from ischemic injury. In the present studies, we investigated the molecular mechanism for the neuro-protective effect of Huwentoxin-I (HWTX-I), a spider toxin selectively blocking N-type voltage-dependent Ca((2+)) channel, on rat models with global cerebral ischemia-reperfusion injury. Our studies demonstrated that HWTX-I could maintain the morphological stability of pyramidal cells in this model. Furthermore, HWTX-I could decrease the concentration of malon-dialdehyde, but increase the activity of superoxide dismutase and glutathione peroxidase. It also reduced the expression level of related factors of Fas and tumor necrosis factor death receptor apoptosis pathways in the hippocampus. In summary, HWTX-I has an obvious neuroprotective effect, which may act through its inhibition on a certain apoptosis pathway.
Wang YR, et al. (2007) Effect of Huwentoxin-I on the Fas and TNF apoptosis pathway in the hippocampus of rat with global cerebral ischemia. Toxicon. PMID: 17900647
The present study was undertaken to elucidate the antinociceptive effect of intrathecal administration of huwentoxin-I (HWTX-I), a N-type calcium channel blocker from the venom of the Chinese bird spider Ornithoctonus huwena (Wang) [=Selenocosmia huwena wang], by comparison with omega-Conotoxin-MVIIA (omega-CTX-MVIIA) and morphine hydrochloride in the formalin test in conscious rats. Similar to omega-CTX-MVIIA and morphine, intrathecal pre-treatment with HWTX-I resulted in suppression of nociceptive behavior in a dose-dependent manner. The ED50 values of HWTX-I and omega-CTX-MVIIA were 0.28 and 0.19 microg/kg, respectively. It was also found that, at lower doses (0.1 and 0.5 microg/kg), the antinociceptive effect of HWTX-I was identical to that of omega-CTX-MVIIA, while omega-CTX-MVIIA acted more remarkably than HWTX-I at higher dose (1.0 microg/kg). However, the antinociception induced by omega-CTX-MVIIA were companied with motor dysfunction, and these side-effects became more evident with the doses of omega-CTX-MVIIA increasing. In contrast, HWTX-I did not show these side-effects at the doses of 0.5-1.0 microg/kg. Compared with HWTX-I and omega-CTX-MVIIA, the analgesic effect of intrathecal morphine hydrochloride was initiated faster, but lasted for a shorter time (about 2-3 h at 1.0 microg/kg) than that of HWTX-I and omega-CTX-MVIIA (about 4- 5 h at 1.0 microg/kg). Therefore, the present results show that, like omega-CTX-MVIIA, the intrathecal administration of HWTX-I is effective in antinociception in the rat model of the formalin test.
Chen JQ., et al. (2005) Antinociceptive effects of intrathecally administered huwentoxin-I, a selective N-type calcium channel blocker, in the formalin test in conscious rats. PMID: 15581678
Huwentoxin-I (HWTX-I), a 3.75 kDa peptide toxin isolated from the venom of the spider Selenocosmia huwena, was found to be a reversible presynaptic inhibitor by our previous work. Using whole-cell patch clamp methods, we found that HWTX-I had no significant effect on the TTX-sensitive Na(+) current or the delayed rectifier K(+) current (K(r)) in low-serum medium cultured NG108-15 cells, but High-Voltage-Activated Ca(2+) channel expressed in prostaglandin E(1) differentiated NG108-15 cells could be potently inhibited by HWTX-I (EC(50) approximately 100 nM), while it hardly affected low-voltage-activated Ca(2+) channel. Among types of high-voltage-activated Ca(2+) channel, HWTX-I selectively inhibited N-type Ca(2+) channel and had only very weak effect on L-type Ca(2+) channel in prostaglandin E(1) differentiated NG108-15 cells.
Peng, K., et al. (2001) The effect of Huwentoxin-I on Ca(2+) channels in differentiated NG108-15 cells, a patch-clamp study, Toxicon. PMID: 11024489
Three different types of isolated nerve-synapse preparations, guinea pig ileum, rat vas deferens and toad heart, were used to investigate the physiological activity of Huwentoxin-1, a neurotoxin from the venom of the spider Selenocosmia huwena. The twitch response of isolated guinea pig ileum induced by electrical stimulus can be inhibited by HWTX-I. After blockage, contraction of the ileum can be induced by exogenously applied acetylcholine. HWTX-I caused the inhibition of the twitch response to electrical nerve stimulation in the rat vas deferens. After the twitch was completely inhibited, noradrenaline triggered rhythmic contraction of the vas deferens. The inhibitory effect on heart of toad induced by stimulating sympathetic-vagus nerve can be reversed by HWTX-I, although exogenously applied acetylcholine still acts as an effective inhibitor. All of these results support the conclusion that HWTX-I has the presynaptic activity that effects the release of neurotransmitter from the nerve endings of both the cholinergic synapse and the adrenergic synapse.
Liang, S. P., et al. (2000) The presynaptic activity of huwentoxin-I, a neurotoxin from the venom of the chinese bird spider Selenocosmia huwena, Toxicon. PMID: 10736477
Huwentoxin-1 (HWTX-I) is a neurotoxic peptide purified from the venom of the Chinese bird spider Selenocosmia huwena. The effects of HWTX-I on neuromuscular transmission of vertebrate skeletal muscle have been investigated by means of twitch tension and electrophysiological techniques. On isolated mouse phrenic nerve-hemidiaphragm preparations, HWTX-I blocked the twitch responses to indirect, but not to direct, muscle stimulation. The time needed for complete block of the neuromuscular transmission was dose dependent. The transmission could be mostly restored by prolonged repeated washing with Tyrode’s solution. If the preparation was pretreated with D-tubocurarine and then immersed in a mixed solution of D-tubocurarine and HWTX-I, the washout time necessary to restore the neuromuscular transmission was significantly decreased. Intracellular recording at the end-plate region of frog sartorius muscle revealed that HWTX-I could synchronously reduce the amplitude of the acetylcholine potential induced by ionophoretic application of acetylcholine as well as the amplitude of the end-plate potential evoked by nerve stimulation. Both of these effects eventually disappeared; however, both could be restored by prolonged washing. Experiments on Xenopus embryonic myocytes indicated that HWTX-I reduced the open probability of acetylcholine-induced channel activity, and finally blocked the channel. All of these results demonstrated that HWTX-I was a peptide neurotoxin and the postsynaptic nicotinic acetylcholine receptor was its site of action.
Zhou, P. A., et al. (1997) Blockade of neuromuscular transmission by huwentoxin-I, purified from the venom of the Chinese bird spider Selenocosmia huwena, Toxicon. PMID: 9028007
By means of reverse phase and ion-exchange high performance liquid chromatography, a neurotoxic peptide named huwentoxin-I was purified from the venom of the Chinese bird spider Selenocosmia huwena. The intraperitoneal and intracisternal LD50 in mice of the toxin were 0.70 mg/kg and 9.40 micrograms/kg, respectively. This toxin at the concentration of 1 x 10(-5) g/ml can irreversibly block the neuromuscular transmission of the isolated mouse phrenic nerve-diaphragm preparation in 13.4 +/- 1.3 min (mean +/- S.D., n = 5). The isoelectric point is 8.95 determined by isoelectric focusing electrophoresis. It consists of 33 amino acids including 6 Cys and 6 Lys determined by amino acid analysis. The complete amino sequence of huwentoxin-1 was determined. The N-terminal and C-terminal residues were Ala and Leu, respectively. The primary structure showed partial homology with that of mu-agatoxins from the funnel-web spider Agelenopsis aperta.
Liang, S. P., et al. (1993) Properties and amino acid sequence of huwentoxin-I, a neurotoxin purified from the venom of the Chinese bird spider Selenocosmia huwena, Toxicon. PMID: 8212049
