Phoneutria nigriventer toxin-3

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Phoneutria nigriventer toxin-3 is more commonly referred to as PhTx3.

The PhTx3 neurotoxin is a broad-spectrum calcium channel blocker that inhibits glutamate release, calcium uptake and also glutamate uptake in synaptosomes. [1] Currently, it is known to naturally occur only in the venom of the spider Phoneutria nigriventer , also known as the Brazilian Wandering spider.

Studies

Many studies have been done on this neurotoxin, including one regarding its effect on the release of 3H-acetylcholine, [2] and one comparing the effect with other toxins used by Phoneutria nigriventer. [1]

Another study made the following claims: [3]

NEUROTOXINS can help the understanding of mechanisms involved in neurotransmission. We here report that two neurotoxin isoforms, Tx3-3 and Tx3-4 obtained from the venom of the spider Phoneutria nigriventer inhibited the 45 Ca2+ influx in rat cortical synaptosomes induced by the scorpion venom tityustoxin. The IC50 for Tx3-3 and Tx3-4 were 0.32 and 7.9 nM, respectively. The neurotoxins Tx3-3 and Tx3-4 are very effective in inhibiting 45 Ca2+ influx and they should be useful in studies involving Ca2+-dependent processes.

A study done at the Universidade Federal de Minas Gerais stated this: [4]

The toxic fraction, Phoneutria nigriventer toxin-3 (PhTx3), abolished Ca2+-dependent glutamate release, but did not alter Ca2+-independent secretion of glutamate when rat brain cortical synaptosomes were depolarized with 33 mM KCl. This effect was most likely due to interference with the entry of calcium through voltage-gated calcium channels, because PhTx3 reduced by 50% the increase in intrasynaptosomal free calcium induced by membrane depolarization, and did not affect the release of glutamate evoked by a calcium ionophore (ionomycin). A polypeptide (Tx3-3) present in the PhTx3 fraction reproduced the effects of the PhTx3 fraction on transmitter release and intrasynaptosomal free calcium in the low nanomolar range. We compared the alterations produced by the Tx3-3 with the actions of toxins known to block calcium channels coupled to exocytosis: the results indicated that the Tx3-3 inhibition of glutamate release and intrasynaptosomal calcium resemble that observed with w-conotoxin MVIIC. We suggest that the Tx3-3 is a calcium-channel antagonist that blocked glutamate exocytosis.

Related Research Articles

<i>Phoneutria</i> Genus of spiders

Phoneutria is a genus of spiders in the family Ctenidae of potential medical significance to humans. They are mainly found in northern South America, with one species in Central America. Members of the genus are commonly referred to as Brazilian wandering spiders. Other English names include armed spiders and banana spiders.

Neurotoxin Toxin harmful to nervous tissue

Neurotoxins are toxins that are destructive to nerve tissue. Neurotoxins are an extensive class of exogenous chemical neurological insults that can adversely affect function in both developing and mature nervous tissue. The term can also be used to classify endogenous compounds, which, when abnormally contacted, can prove neurologically toxic. Though neurotoxins are often neurologically destructive, their ability to specifically target neural components is important in the study of nervous systems. Common examples of neurotoxins include lead, ethanol, glutamate, nitric oxide, botulinum toxin, tetanus toxin, and tetrodotoxin. Some substances such as nitric oxide and glutamate are in fact essential for proper function of the body and only exert neurotoxic effects at excessive concentrations.

Neuromuscular junction Junction between the axon of a motor neuron and a muscle fiber

A neuromuscular junction is a chemical synapse between a motor neuron and a muscle fiber.

Synaptic vesicle Neurotransmitters that are released at the synapse

In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell. The area in the axon that holds groups of vesicles is an axon terminal or "terminal bouton". Up to 130 vesicles can be released per bouton over a ten-minute period of stimulation at 0.2 Hz. In the visual cortex of the human brain, synaptic vesicles have an average diameter of 39.5 nanometers (nm) with a standard deviation of 5.1 nm.

A latrotoxin is a high-molecular mass neurotoxin found in the venom of spiders of the genus Latrodectus and also found in the venom of spider species, Steatoda nobilis. Latrotoxins are the main active components of the venom and are responsible for the symptoms of latrodectism.

<i>Phoneutria nigriventer</i> Species of arachnid

Phoneutria nigriventer is a species of medically significant spider in the family Ctenidae, found in South America. Along with other members of the genus, they are often referred to as Brazilian wandering spiders.

Taicatoxin (TCX) is a snake toxin that blocks voltage-dependent L-type calcium channels and small conductance Ca2+-activated K+ channels. The name taicatoxin (TAIpan + CAlcium + TOXIN) is derived from its natural source, the taipan snake, the site of its action, calcium channels, and from its function as a toxin. Taicatoxin was isolated from the venom of Australian taipan snake, Oxyuranus scutellatus scutellatus. TCX is a secreted protein, produced in the venom gland of the snake.

Tityustoxin is a toxin found in the venom of scorpions from the subfamily Tityinae. By binding to voltage-dependent sodium ion channels and potassium channels, they cause sialorrhea, lacrimation and rhinorrhea.

The P-type calcium channel is a type of voltage-dependent calcium channel. Similar to many other high-voltage-gated calcium channels, the α1 subunit determines most of the channel's properties. The 'P' signifies cerebellar Purkinje cells, referring to the channel's initial site of discovery. P-type calcium channels play a similar role to the N-type calcium channel in neurotransmitter release at the presynaptic terminal and in neuronal integration in many neuronal types.

Tx2-6 is a toxin found in the venom of the Brazilian wandering spider, Phoneutria nigriventer(Keyserling). It is a peptide of 48 residues, molecular weight 5291.3. This peptide is cleaved from a longer precursor with a signal peptide and a glutamine-rich propeptide. It can cause priapism. Tests on rats indicate that the toxin causes nitric oxide release, and its effect on erection is blocked by the nitric oxide synthase inhibitor L-NAME. However, it fully restored erectile function in rats developing hypertension due to injection of deoxycorticosterone acetate. A study is underway at the Medical College of Georgia looking at possible uses for the chemical in erectile dysfunction medication. Scientists and Gregory Ochs are collaborating on this study.

Agatoxin

Agatoxins are a class of chemically diverse polyamine and peptide toxins which are isolated from the venom of various spiders. Their mechanism of action includes blockade of glutamate-gated ion channels, voltage-gated sodium channels, or voltage-dependent calcium channels. Agatoxin is named after the funnel web spider which produces a venom containing several agatoxins. There are different agatoxins. The ω‎-agatoxins are approximately 100 amino acids in length and are antagonists of voltage-sensitive calcium channels and also block the release of neurotransmitters. For instance, the ω‎-agatoxin 1A is a selective blocker and will block L-type calcium channels whereas the ω‎-agatoxin 4B will inhibit voltage sensitive P-type calcium channels. The μ‎-agatoxins only act on insect voltage-gated sodium channels.

Argiotoxins represent a class of polyamine toxins isolated from the orb-weaver spider.

Philanthotoxins are components of the venom of the Egyptian solitary wasp Philanthus triangulum, commonly known as the European beewolf. Philanthotoxins are polyamine toxins, a group of toxins isolated from the venom of wasps and spiders which immediately but reversibly paralyze their prey.. δ-philanthotoxin, also known as PhTX-433, is the most active philanthotoxin that can be refined from the venom. PhTX-433 functions by non-selectively blocking excitatory neurotransmitter ion channels, including nicotinic acetylcholine receptors (nAChRs) and ionotropic glutamate receptors (iGluRs). Synthetic analogues, including PhTX-343 and PhTX-12, have been developed to improve selectivity. While the IC50 values of philanthotoxins varies between analogues and receptor subunit composition, the IC50 value of PhTX-433 at the iGluR AMPA receptor naturally expressed in locust leg muscle is 18 μM and the IC50 value at rat nAChRs is 1 μM.

Phoneutria keyserlingi is a species of spiders in the family Ctenidae, found in Brazil.

Oxotoxins, or oxytoxins, are a group of neurotoxins present in the venom of lynx spiders belonging to the genus Oxyopes, hence the name oxytoxin. They are disulfide-rich peptides. Only two types are so far reported from two different species, the larger oxytoxin 1 (OxyTx1) from Oxyopes kitabensis, and the smaller oxytoxin 2 (OxyTx2) from Oxyopes lineatus. OxyTx1, the first known oxytoxin, was discovered in 2002. It was found to enhance the lethal efficacy of the spider venom by acting together with oxyopinins. It is composed of 69 amino acid residue, which are cross-linked by five disulfide bridges. It is a large peptide having a molecular mass of 8059.2 Da; but shows the size of 9,109.4 Da due to the presence of disulfide bridges. It is a potent insecticide, but non-toxic to mice up to 1 μg/20-g mouse. It acts synergistically with oxyopinins of the same venom to increase the insecticidal effect.

Tamulotoxin is a venomous neurotoxin from the Indian Red Scorpion.

The pathophysiology of a spider bite is due to the effect of its venom. A spider envenomation occurs whenever a spider injects venom into the skin. Not all spider bites inject venom – a dry bite, and the amount of venom injected can vary based on the type of spider and the circumstances of the encounter. The mechanical injury from a spider bite is not a serious concern for humans. Some spider bites do leave a large enough wound that infection may be a concern. However, it is generally the toxicity of spider venom that poses the most risk to human beings; several spiders are known to have venom that can cause injury to humans in the amounts that a spider will typically inject when biting.

Crotoxin (CTX) is the main toxic compound in the snake venom of the South American rattlesnake, Crotalus durissus terrificus. Crotoxin is a heterodimeric beta-neurotoxin, composed of an acidic, non-toxic and non-enzymatic subunit (CA), and a basic, weakly toxic, phospholipase A2 protein (CB). This neurotoxin causes paralysis by both pre- and postsynaptic blocking of acetylcholine signalling.

PhTx-2 is a toxic fraction of the venom of the Brazilian wandering spider Phoneutria nigriventer.

PhTx-1 is a toxic fraction isolated from the venom of the Brazilian wandering spider Phoneutria nigriventer.

References

  1. 1 2 Pinheiro, Ana C.N.; Gomez, Rodrigo S.; Massensini, Andre R.; Cordeiro, Marta N.; Richardson, Michael; Romano-Silva, Marco A.; Prado, Marco Antonio M.; Marco, Luiz De; Gomez, Marcus V. (October 2006). "Neuroprotective effect on brain injury by neurotoxins from the spider Phoneutria nigriventer". Neurochemistry International. 49 (5): 543–547. doi:10.1016/j.neuint.2006.04.009. PMID   16759753. S2CID   33511610. INIST:18035910.
  2. Gomez, R.S.; Casali, T.A.A.; Romano-Silva, M.A.; Cordeiro, M.N.; Diniz, C.R.; Moraes-Santos, T.; Prado, M.A.M.; Gomez, M.V. (August 1995). "The effect of PhTx3 on the release of 3H-acetylcholine induced by tityustoxin and potassium in brain cortical slices and myenteric plexus". Neuroscience Letters. 196 (1–2): 131–133. doi:10.1016/0304-3940(95)11843-L. PMID   7501242. S2CID   12820501.
  3. Miranda, Debora Marques; Romano-Silva, Marco Aurélio; Kalapothakis, Evanguedes; Diniz, Carlos Ribeiro; Cordeiro, Marta Nascimento; Santos, Tasso Moraes; Antonio, Marco; Prado, Máximo; Gomez, Marcus Vinicius (May 1998). "Phoneutria nigriventer toxins block tityustoxin-induced calcium influx in synaptosomes". NeuroReport. 9 (7): 1371–1373. doi:10.1097/00001756-199805110-00022. PMID   9631431. S2CID   37009866.
  4. Prado, M A; Guatimosim, C; Gomez, M V; Diniz, C R; Cordeiro, M N; Romano-Silva, M A (15 February 1996). "A novel tool for the investigation of glutamate release from rat cerebrocortical synaptosomes: the toxin Tx3-3 from the venom of the spider Phoneutria nigriventer". Biochemical Journal. 314 (Pt 1): 145–150. doi:10.1042/bj3140145. PMC   1217017 . PMID   8660275.