PhTx4, a new class of toxins from Phoneutria nigriventer spider venom, inhibits the glutamate uptake in rat brain synaptosomes

Mafra, Roberta Amaral; Figueiredo, Suely G.; Diniz, Carlos R.; Cordeiro, Marta N.; Cruz, Jáder Santos; Lima, Maria Elena de

doi:10.1016/s0006-8993(99)01472-9

Cited by 36 publications

(12 citation statements)

References 29 publications

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“…However, the specificity of PhTx3-4 for glutamate transporters is unknown. The toxin PhTx4-7 from the same spider seems to produce similar effects [88,89].…”

Section: Spptxs Acting On Glutamate Receptorsmentioning

confidence: 97%

Pharmacologically active spider peptide toxins

Corzo

Escoubas

2003

Cellular and Molecular Life Sciences (CMLS)

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Advances in mass spectrometry and peptide biochemistry coupled to modern methods in electrophysiology have permitted the isolation and identification of numerous novel peptide toxins from animal venoms in recent years. These advances have also opened up the field of spider venom research, previously unexplored due to methodological limitations. Many peptide toxins from spider venoms share structural features, amino acid composition and consensus sequences that allow them to interact with related classes of cellular receptors. They have become increasingly useful agents for the study of voltage-sensitive and ligand-gated ion channels and the discrimination of their cellular subtypes. Spider peptide toxins have also been recognized as useful agents for their antimicrobial properties and the study of pore formation in cell membranes. Spider peptide toxins with nanomolar affinities for their receptors are thus promising pharmacological tools for understanding the physiological role of ion channels and as leads for the development of novel therapeutic agents and strategies for ion channel-related diseases. Their high insecticidal potency can also make them useful probes for the discovery of novel insecticide targets in the insect nervous system or for the development of genetically engineered microbial pesticides.

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“…However, the specificity of PhTx3-4 for glutamate transporters is unknown. The toxin PhTx4-7 from the same spider seems to produce similar effects [88,89].…”

Section: Spptxs Acting On Glutamate Receptorsmentioning

confidence: 97%

Pharmacologically active spider peptide toxins

Corzo

Escoubas

2003

Cellular and Molecular Life Sciences (CMLS)

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“…Most of the toxins that have been purified from this venom seem to act on ionic channels, including those for sodium (Araujo et al, 1993;De Lima et al, 2007;Martin-Moutot et al, 2006;Matavel et al, 2002), calcium (Dos Santos et al, 2002;Guatimosim et al, 1997;Leão et al, 2000;Vieira et al, 2005) and potassium (Kushmerick et al, 1999). Some of these toxins have insecticidal activity (for a review see De Lima et al, 2007), interfer with the uptake of L-glutamate on synaptosomes of rat brain (Mafra et al, 1999) and inhibit NMDA-evoked currents in rat hippocampal neurons (Figueiredo et al, 2001). A semi-purified toxic fraction called PhTx2 releases acetylcholine from rat cerebrocortical synaptosomes (Moura et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Tx2-6 toxin of the Phoneutria nigriventer spider potentiates rat erectile function

Nunes

Costa‐Goncalves

Lanza

et al. 2008

Toxicon

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The venom of the spider Phoneutria nigriventer contains several toxins that have bioactivity in mammals and insects. Accidents involving humans are characterized by various symptoms including penile erection. Here we investigated the action of Tx2-6, a toxin purified from the P. nigriventer spider venom that causes priapism in rats and mice. Erectile function was evaluated through changes in intracavernosal pressure/mean arterial pressure ratio (ICP/MAP) during electrical stimulation of the major pelvic ganglion (MPG) of normotensive and deoxycorticosterone-acetate (DOCA)-salt hypertensive rats. Nitric oxide (NO) release was detected in cavernosum slices with fluorescent dye (DAF-FM) and confocal microscopy. The effect of Tx2-6 was also characterized after intracavernosal injection of a non-selective nitric oxide synthase (NOS) inhibitor, L-NAME. Subcutaneous or intravenous injection of Tx2-6 potentiated the elevation of ICP/MAP induced by ganglionic stimulation. L-NAME inhibited penile erection and treatment with Tx2-6 was unable to reverse this inhibition. Tx2-6 treatment induced a significant increase of NO release in cavernosum tissue. Attenuated erectile function of DOCA-salt hypertensive rats was fully restored after toxin injection. Tx2-6 enhanced erectile function in normotensive and DOCA-salt hypertensive rats, via the NO pathway. Our studies suggest that Tx2-6 could be important for development of new pharmacological agents for treatment of erectile dysfunction.

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“…Both pyramidal dendrites and granule dendrites possess N -methyl- d -aspartate (NMDA) receptors, and Na + and Ca 2+ channels, and therefore the possibility of being affected by ion channel acting-neuropeptides of PNV [3] is not excluded. Neuropeptides of PNV contain a calcium channel antagonist that blocks glutamate exocytosis but also inhibits glutamate uptake [35,36,37] in synaptosomes. VEGF modulates NMDA receptor activity in cerebellar granule cells through Src-family kinases before synapse formation [38] reduces calcium influx via inhibition of the Ca 2+ channels in rat hippocampal neurons [39] and controls epileptic activity by influencing glutamatergic and gamma-aminobutyric acid (GABA)ergic neurotransmission [40,41].…”

Section: Discussionmentioning

confidence: 99%

Expression of VEGF and Flk-1 and Flt-1 Receptors during Blood-Brain Barrier (BBB) Impairment Following Phoneutria nigriventer Spider Venom Exposure

Mendonça

Soares

Stávale

et al. 2013

Toxins

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Apart from its angiogenic and vascular permeation activity, the vascular endothelial growth factor (VEGF) has been also reported as a potent neuronal protector. Newborn rats with low VEGF levels develop neuron degeneration, while high levels induce protective mechanisms in several neuropathological conditions. Phoneutria nigriventer spider venom (PNV) disrupts the blood-brain barrier (BBB) and causes neuroinflammation in central neurons along with excitotoxic signals in rats and humans. All these changes are transient. Herein, we examined the expression of VEGF and its receptors, Flt-1 and Flk-1 in the hippocampal neurons following envenomation by PNV. Adult and neonatal rats were evaluated at time limits of 2, 5 and 24 h. Additionally, BBB integrity was assessed by measuring the expression of occludin, β-catenin and laminin and neuron viability was evaluated by NeuN expression. VEGF, Flt-1 and Flk-1 levels increased in PNV-administered rats, concurrently with respective mRNAs. Flt-1 and Flk-1 immunolabeling was nuclear in neurons of hippocampal regions, instead of the VEGF membrane-bound typical location. These changes occurred simultaneously with the transient decreases in BBB-associated proteins and NeuN positivity. Adult rats showed more prominent expressional increases of the VEGF/Flt-1/Flk-1 system and earlier recovery of BBB-related proteins than neonates. We conclude that the reactive expressional changes seen here suggest that VEGF and receptors could have a role in the excitotoxic mechanism of PNV and that such role would be less efficient in neonate rats.

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PhTx4, a new class of toxins from Phoneutria nigriventer spider venom, inhibits the glutamate uptake in rat brain synaptosomes

Cited by 36 publications

References 29 publications

Pharmacologically active spider peptide toxins

Pharmacologically active spider peptide toxins

Tx2-6 toxin of the Phoneutria nigriventer spider potentiates rat erectile function

Expression of VEGF and Flk-1 and Flt-1 Receptors during Blood-Brain Barrier (BBB) Impairment Following Phoneutria nigriventer Spider Venom Exposure

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