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

K. P. Nunes, A. Costa-Gonçalves, L. F. Lanza, S. F. Cortes, M. N. Cordeiro, M. Richardson, A. M.C. Pimenta, R Clinton Webb, R. Leite, M. E. De Lima

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1197-1206
Number of pages10
JournalToxicon
Volume51
Issue number7
DOIs
StatePublished - Jun 1 2008

Fingerprint

Spiders
Rats
Desoxycorticosterone
Spider Venoms
Penile Erection
Nitric Oxide
Acetates
Salts
Arterial Pressure
Priapism
Pressure
Injections
Mammals
Confocal microscopy
Erectile Dysfunction
Subcutaneous Injections
Bioactivity
Tx2 neurotoxin
Fluorescent Dyes
Confocal Microscopy

Keywords

  • Erectile function
  • Nitric oxide
  • Phoneutria nigriventer
  • Tx2-6 toxin

ASJC Scopus subject areas

  • Toxicology

Cite this

Nunes, K. P., Costa-Gonçalves, A., Lanza, L. F., Cortes, S. F., Cordeiro, M. N., Richardson, M., ... De Lima, M. E. (2008). Tx2-6 toxin of the Phoneutria nigriventer spider potentiates rat erectile function. Toxicon, 51(7), 1197-1206. https://doi.org/10.1016/j.toxicon.2008.02.010

Tx2-6 toxin of the Phoneutria nigriventer spider potentiates rat erectile function. / Nunes, K. P.; Costa-Gonçalves, A.; Lanza, L. F.; Cortes, S. F.; Cordeiro, M. N.; Richardson, M.; Pimenta, A. M.C.; Webb, R Clinton; Leite, R.; De Lima, M. E.

In: Toxicon, Vol. 51, No. 7, 01.06.2008, p. 1197-1206.

Research output: Contribution to journalArticle

Nunes, KP, Costa-Gonçalves, A, Lanza, LF, Cortes, SF, Cordeiro, MN, Richardson, M, Pimenta, AMC, Webb, RC, Leite, R & De Lima, ME 2008, 'Tx2-6 toxin of the Phoneutria nigriventer spider potentiates rat erectile function', Toxicon, vol. 51, no. 7, pp. 1197-1206. https://doi.org/10.1016/j.toxicon.2008.02.010
Nunes KP, Costa-Gonçalves A, Lanza LF, Cortes SF, Cordeiro MN, Richardson M et al. Tx2-6 toxin of the Phoneutria nigriventer spider potentiates rat erectile function. Toxicon. 2008 Jun 1;51(7):1197-1206. https://doi.org/10.1016/j.toxicon.2008.02.010
Nunes, K. P. ; Costa-Gonçalves, A. ; Lanza, L. F. ; Cortes, S. F. ; Cordeiro, M. N. ; Richardson, M. ; Pimenta, A. M.C. ; Webb, R Clinton ; Leite, R. ; De Lima, M. E. / Tx2-6 toxin of the Phoneutria nigriventer spider potentiates rat erectile function. In: Toxicon. 2008 ; Vol. 51, No. 7. pp. 1197-1206.
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AU - Cordeiro, M. N.

AU - Richardson, M.

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AB - 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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