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Nitric oxide-induced vasorelaxation in response to PnTx2-6 toxin from Phoneutria nigriventer spider in rat cavernosal tissue.

Abstract

INTRODUCTION
Priapism is one of several symptoms observed in accidental bites by the spider Phoneutria nigriventer. The venom of this spider is comprised of many toxins, and the majority has been shown to affect excitable ion channels, mainly sodium (Na(+) ) channels. It has been demonstrated that PnTx2-6, a peptide extracted from the venom of P. nigriventer, causes erection in anesthetized rats and mice.
AIM
We investigated the mechanism by which PnTx2-6 evokes relaxation in rat corpus cavernosum.
MAIN OUTCOME MEASURES
PnTx2-6 toxin potentiates nitric oxide (NO)-dependent cavernosal relaxation.
METHODS
Rat cavernosal strips were incubated with bretylium (3 × 10(-5) M) and contracted with phenylephrine (PE; 10(-5) M). Relaxation responses were evoked by electrical field stimulation (EFS) or sodium nitroprusside (SNP) before and after 4 minutes of incubation with PnTx2-6 (10(-8) M). The effect of PnTx2-6 on relaxation induced by EFS was also tested in the presence of atropine (10(-6) M), a muscarinic receptor antagonist, N-type Ca(2+) channel blockers (ω-conotoxin GVIA, 10(-6) M) and sildenafil (3 × 10(-8) M). Technetium99m radiolabeled PnTx2-6 subcutaneous injection was administrated in the penis.
RESULTS
Whereas relaxation induced by SNP was not affected by PnTx2-6, EFS-induced relaxation was significantly potentiated by this toxin as well as PnTx2-6 plus SNP. This potentiating effect was further increased by sildenafil, not altered by atropine, however was completely blocked by the N-type Ca(2+) channels. High concentrated levels of radiolabeled PnTx2-6 was specifically found in the cavernosum tissue, suggesting PnTx2-6 is an important toxin responsible for P. nigriventer spider accident-induced priapism.
CONCLUSION
We show that PnTx2-6 slows Na(+) channels inactivation in nitrergic neurons, allowing Ca(2+) influx to facilitate NO/cGMP signalling, which promotes increased NO production. In addition, this relaxation effect is independent of phosphodiesterase enzyme type 5 inhibition. Our data displays PnTx2-6 as possible pharmacological tool to study alternative treatments for erectile dysfunction.

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  • Authors

    Nunes KP, Cordeiro MN, Richardson M, Borges MN, Diniz SO, Cardoso VN, Tostes R, De Lima ME, Webb RC, Leite R

    Source

    The journal of sexual medicine 7:12 2010 Dec pg 3879-88

    MeSH

    Animals
    Atropine
    Calcium Channel Blockers
    Calcium Channels, N-Type
    Electric Stimulation
    Male
    Muscarinic Antagonists
    Neuropeptides
    Neurotoxins
    Nitric Oxide
    Nitric Oxide Donors
    Nitroprusside
    Penis
    Phosphodiesterase 5 Inhibitors
    Piperazines
    Purines
    Rats
    Rats, Sprague-Dawley
    Rats, Wistar
    Spider Venoms
    Sulfones
    Technetium
    Vasodilation
    omega-Conotoxin GVIA

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    20722794