PnPP-19, a Synthetic and Nontoxic Peptide Designed from a Phoneutria nigriventer Toxin, Potentiates Erectile Function via NO/cGMP
PnPP-19, a Synthetic and Nontoxic Peptide Designed from a Phoneutria nigriventer Toxin, Potentiates Erectile Function via NO/cGMP
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DOI：
10.1016/j.juro.2015.06.081
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发表时间：
2015-11-01
影响因子：
6.6
通讯作者：
de Lima, Maria Elena
中科院分区：
文献类型：
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作者：
Silva, Carolina Nunes;Nunes, Kenia Pedrosa;de Lima, Maria Elena
目的：我们设计了一个肽，PnPP-19，包含潜在的活性核心的Phoneutria nigriventer天然毒素PnTx 2 -6。我们研究了它对勃起功能的作用，以及它的毒性和免疫原性。材料和方法：勃起功能的海绵体内压力，平均动脉压比在电场刺激大鼠盆神经节。用苯肾上腺素收缩海绵体条，用或不用PnPP-19（10（-8）M）通过电场刺激诱导松弛。通过对非洲爪蟾卵母细胞和背根神经节细胞上的转染通道进行电生理学筛选来评估对钠通道的活性。通过间接酶联免疫吸附试验检测先前用肽处理的小鼠中的抗体。结果：PnPP-19在体内和离体条件下均能增强4 Hz和8 Hz的勃起功能。它在小鼠中显示无毒性和低免疫原性，并且不影响钠通道或大鼠心脏。PnPP-19在8Hz下增加环鸟苷一磷酸水平。L-NAME（10（-4）M）可抑制这种作用。勃起功能被神经元型一氧化氮合酶的选择性抑制剂7-硝基吲唑（10（-5）M）部分抑制。结论：PnPP-19通过一氧化氮/环磷酸鸟苷途径增强体内和体外勃起。它不影响钠通道或大鼠心脏，显示无毒性和低免疫原性。这些发现使其成为治疗勃起功能障碍的一种有希望的候选新药。
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.