Increased cavernosal relaxation by Phoneutria nigriventer toxin, PnTx2-6, via activation at NO/cGMP signaling.
Increased cavernosal relaxation by Phoneutria nigriventer toxin, PnTx2-6, via activation at NO/cGMP signaling.
复制标题
DOI：
10.1038/ijir.2011.47
复制
发表时间：
2012-03
影响因子：
2.6
通讯作者：
Webb, R. C.
中科院分区：
文献类型：
--
作者：
Nunes, K. P.;Wynne, B. M.;Cordeiro, M. N.;Borges, M. H.;Richardson, M.;Leite, R.;DeLima, M. E.;Webb, R. C.
糖尿病患者的勃起功能障碍机制是多因素的，并且经常导致对当前治疗的抵抗。动物毒素已被用作研究阴茎勃起的药理学工具。涉及Phoneutria nigriventer蜘蛛毒液的人类事故的特征是阴茎异常勃起。我们推测PnTx 2 -6通过增加cGMP增强糖尿病小鼠海绵体松弛。这种效应是nNOS依赖性的。在存在或不存在PnTx 2 -6（10−8 M）的情况下，用苯肾上腺素（10−5 M）收缩海绵体条，并通过电场刺激（EFS，20 V，1-32 Hz）放松。nNOS和eNOS knocaut（KO）小鼠的海绵体条，以及nNOS抑制剂（10− 5 M），用于评估这种酶在PnTx 2 -6诱发的增强效应中的作用。在存在或不存在L-NAME（10− 4 M）和ω-芋螺毒素GVIA（10− 6 M）（一种N型钙通道抑制剂）的情况下，用PnTx 2 -6刺激后测定组织cGMP水平。结果显示PnTx 2 -6增强糖尿病小鼠（65%）和eNOS KO小鼠的海绵体舒张，但不增强nNOS KO小鼠的海绵体舒张。nNOS抑制剂可阻断毒素对阴茎海绵体的舒张作用。cGMP水平通过PnTx 2 -6增加，然而L-NAME以及ω-芋螺毒素GVIA消除这种增强。我们的结论是PnTx 2 -6通过依赖于nNOS的机制促进糖尿病小鼠阴茎舒张，可能是通过增加NO/cGMP的产生。
Erectile dysfunction 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 cGMP. This effect is nNOS dependent. Cavernosal strips were contracted with phenylephrine (10−5 M) and relaxed by electrical field stimulation (EFS, 20V, 1–32 Hz) in the presence or absence of PnTx2-6 (10−8 M).Cavernosal strips from nNOS and eNOS knocaut (KO) mice, besides nNOS inhibitor (10−5M), 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 L-NAME (10−4M) and ω-conotoxin GVIA (10−6M), an N-type calcium channel inhibitor. Results showed 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 PnTx2-6 facilitates penile relaxation in diabetic mice through a mechanism dependent on nNOS, probably via increasing NO/cGMP production.
登录
查看更多内容
影响因子：
56.9
作者：
BURNETT, AL;LOWENSTEIN, CJ;SNYDER, SH
通讯作者：
SNYDER, SH
影响因子：
4.5
作者：
Andrade, Enrico;Villanova, Fabiola;Srougi, Miguel
通讯作者：
Srougi, Miguel
影响因子：
--
作者：
Burnett, AL;Chang, AG;Sezen, SF
通讯作者：
Sezen, SF
DOI：
10.1590/s0036-46652000000100003
发表时间：
2000-01-01
影响因子：
1.9
作者：
Bucaretchi, Fabio;de Deus Reinaldo, Claudia Regina;Vieira, Ronan Jose
通讯作者：
Vieira, Ronan Jose
影响因子：
3.6
作者：
Martin-Moutot, Nicole;Mansuelle, Pascal;Van Renterghem, Catherine
通讯作者：
Van Renterghem, Catherine