PnPP-19, a Synthetic and Nontoxic Peptide Designed from a Phoneutria nigriventer Toxin, Potentiates Erectile Function via NO/cGMP

J Urol. 2015 Nov;194(5):1481-90. doi: 10.1016/j.juro.2015.06.081. Epub 2015 Jun 26.


Purpose: We designed a peptide, PnPP-19, comprising the potential active core of the Phoneutria nigriventer native toxin PnTx2-6. We investigated its role on erectile function, and its toxicity and immunogenicity.

Materials and methods: Erectile function was evaluated by the intracavernous pressure-to-mean arterial pressure ratio during electrical field stimulation on rat pelvic ganglia. Cavernous strips were contracted with phenylephrine and relaxation was induced by electrical field stimulation with or without PnPP-19 (10(-8) M). Activity on sodium channels was evaluated by electrophysiological screening of transfected channels on Xenopus oocytes and dorsal root ganglion cells. Antibodies were detected by indirect enzyme-linked immunosorbent assay in mice previously treated with the peptide. Histopathological studies were performed with mouse organs treated with different doses of PnPP-19.

Results: PnPP-19 was able to potentiate erection at 4 and 8 Hz in vivo and ex vivo. It showed no toxicity and low immunogenicity in mice, and did not affect sodium channels or rat hearts. PnPP-19 increased cyclic guanosine monophosphate levels at 8 Hz. This effect was inhibited by L-NAME (10(-4) M). Erectile function was partially inhibited by 7-nitroindazole (10(-5) M), a selective inhibitor of neuronal nitric oxide synthase.

Conclusions: PnPP-19 potentiates erection in vivo and ex vivo via the nitric oxide/cyclic guanosine monophosphate pathway. It does not affect sodium channels or rat hearts and shows no toxicity and low immunogenicity. These findings make it a promising candidate as a novel drug in the therapy of erectile dysfunction.

Keywords: Phoneutria nigriventer; Tx2-6 protein; chemistry techniques; drug evaluation; penile erection; peptide; preclinical; synthetic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclic GMP / metabolism*
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Erectile Dysfunction / drug therapy*
  • Erectile Dysfunction / physiopathology
  • Male
  • Mice
  • Neuropeptides / pharmacology*
  • Neurotoxins
  • Nitric Oxide Synthase Type I / metabolism*
  • Patch-Clamp Techniques
  • Penile Erection / drug effects*
  • Rats
  • Rats, Sprague-Dawley


  • Neuropeptides
  • Neurotoxins
  • Tx1 neurotoxin
  • Nitric Oxide Synthase Type I
  • Nos1 protein, rat
  • Cyclic GMP