Increased cavernosal relaxation by Phoneutria nigriventer toxin, PnTx2-6, via activation at NO/cGMP signaling

K. P. Nunes, B. M. Wynne, M. N. Cordeiro, M. H. Borges, M. Richardson, R. Leite, M. E. Delima, R Clinton Webb

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Erectile dysfunction (ED) mechanisms in diabetic patients are multifactorial and often lead to resistance to current therapy. Animal toxins have been used as pharmacological tools to study penile erection. Human accidents involving the venom of Phoneutria nigriventer spider are characterized by priapism. We hypothesize that PnTx2-6 potentiates cavernosal relaxation in diabetic mice by increasing cyclic guanosine monophosphate (cGMP). This effect is neuronal nitric oxide synthase (nNOS) dependent. Cavernosal strips were contracted with phenylephrine (10 -5 M) and relaxed by electrical field stimulation (20 V, 1-32 Hz) in the presence or absence of PnTx2-6 (10 -8 M). Cavernosal strips from nNOS- and endothelial nitric oxide synthase (eNOS)-knockout (KO) mice, besides nNOS inhibitor (10 -5 M), were used to evaluate the role of this enzyme in the potentiation effect evoked by PnTx2-6. Tissue cGMP levels were determined after stimulation with PnTx2-6 in presence or absence of N-nitro-L-arginine methyl ester (L-NAME) (10 -4 M) and -conotoxin GVIA (10 -6 M), an N-type calcium channel inhibitor. Results showed that PnTx2-6 enhanced cavernosal relaxation in diabetic mice (65%) and eNOS KO mice, but not in nNOS KO mice. The toxin effect in the cavernosal relaxation was abolished by nNOS inhibitor. cGMP levels are increased by PnTx2-6, however, L-NAME abolished this enhancement as well as -conotoxin GVIA. We conclude that PnTx2-6 facilitates penile relaxation in diabetic mice through a mechanism dependent on nNOS, probably via increasing nitric oxide/cGMP production.

Original languageEnglish (US)
Pages (from-to)69-76
Number of pages8
JournalInternational Journal of Impotence Research
Volume24
Issue number2
DOIs
StatePublished - Mar 1 2012

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Nitric Oxide Synthase Type I
Cyclic GMP
Conotoxins
Knockout Mice
Nitric Oxide Synthase Type III
NG-Nitroarginine Methyl Ester
N-Type Calcium Channels
Priapism
Penile Erection
Spiders
Venoms
Phenylephrine
Erectile Dysfunction
Electric Stimulation
Accidents
4-(3'-di(2-bromoethyl)aminopropionyl)biphenyl
Nitric Oxide
Pharmacology
Enzymes

Keywords

  • NO
  • Phoneutria nigriventer
  • PnTx2-6 toxin
  • cGMP
  • erectile dysfunction

ASJC Scopus subject areas

  • Urology

Cite this

Increased cavernosal relaxation by Phoneutria nigriventer toxin, PnTx2-6, via activation at NO/cGMP signaling. / Nunes, K. P.; Wynne, B. M.; Cordeiro, M. N.; Borges, M. H.; Richardson, M.; Leite, R.; Delima, M. E.; Webb, R Clinton.

In: International Journal of Impotence Research, Vol. 24, No. 2, 01.03.2012, p. 69-76.

Research output: Contribution to journalArticle

Nunes, K. P. ; Wynne, B. M. ; Cordeiro, M. N. ; Borges, M. H. ; Richardson, M. ; Leite, R. ; Delima, M. E. ; Webb, R Clinton. / Increased cavernosal relaxation by Phoneutria nigriventer toxin, PnTx2-6, via activation at NO/cGMP signaling. In: International Journal of Impotence Research. 2012 ; Vol. 24, No. 2. pp. 69-76.
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AU - Nunes, K. P.

AU - Wynne, B. M.

AU - Cordeiro, M. N.

AU - Borges, M. H.

AU - Richardson, M.

AU - Leite, R.

AU - Delima, M. E.

AU - Webb, R Clinton

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AB - Erectile dysfunction (ED) mechanisms in diabetic patients are multifactorial and often lead to resistance to current therapy. Animal toxins have been used as pharmacological tools to study penile erection. Human accidents involving the venom of Phoneutria nigriventer spider are characterized by priapism. We hypothesize that PnTx2-6 potentiates cavernosal relaxation in diabetic mice by increasing cyclic guanosine monophosphate (cGMP). This effect is neuronal nitric oxide synthase (nNOS) dependent. Cavernosal strips were contracted with phenylephrine (10 -5 M) and relaxed by electrical field stimulation (20 V, 1-32 Hz) in the presence or absence of PnTx2-6 (10 -8 M). Cavernosal strips from nNOS- and endothelial nitric oxide synthase (eNOS)-knockout (KO) mice, besides nNOS inhibitor (10 -5 M), were used to evaluate the role of this enzyme in the potentiation effect evoked by PnTx2-6. Tissue cGMP levels were determined after stimulation with PnTx2-6 in presence or absence of N-nitro-L-arginine methyl ester (L-NAME) (10 -4 M) and -conotoxin GVIA (10 -6 M), an N-type calcium channel inhibitor. Results showed that PnTx2-6 enhanced cavernosal relaxation in diabetic mice (65%) and eNOS KO mice, but not in nNOS KO mice. The toxin effect in the cavernosal relaxation was abolished by nNOS inhibitor. cGMP levels are increased by PnTx2-6, however, L-NAME abolished this enhancement as well as -conotoxin GVIA. We conclude that PnTx2-6 facilitates penile relaxation in diabetic mice through a mechanism dependent on nNOS, probably via increasing nitric oxide/cGMP production.

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