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

International Journal of Impotence Research volume 24, pages 69–76 (2012)Cite this article

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 ω-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 ω-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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Acknowledgements

This work was supported by grants from NIH (RO1-HL083685) and AHA in USA and grants from CAPES, CNPq, FAPEMIG and INCTTOX-FAPESP in Brazil. Dr Nunes is supported by AHA Post-Doctoral fellowship.

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Authors and Affiliations

  1. Department of Biochemistry, Biological Science Institute Federal University of Minas Gerais Gerais, Belo Horizonte, Brazil

    K P Nunes & M E DeLima

  2. School of Medicine—Department of Physiology, Medical College of Georgia, Augusta, GA, USA

    K P Nunes, B M Wynne & R C Webb

  3. Ezequiel Dias Foundation, Belo Horizonte, Brazil

    M N Cordeiro, M H Borges & M Richardson

  4. School of Pharmacy—Federal University of Ouro Preto, Ouro Preto, Brazil

    R Leite

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  1. K P Nunes
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Correspondence to K P Nunes.

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Nunes, K., Wynne, B., Cordeiro, M. et al. Increased cavernosal relaxation by Phoneutria nigriventer toxin, PnTx2-6, via activation at NO/cGMP signaling. Int J Impot Res 24, 69–76 (2012). https://doi.org/10.1038/ijir.2011.47

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