Hurt K Joseph, Sezen Sena F, Champion Hunter C, Crone Julie K, Palese Michael A, Huang Paul L, Sawa Akira, Luo Xiaojiang, Musicki Biljana, Snyder Solomon H, Burnett Arthur L
Department of Urology, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3440-3. doi: 10.1073/pnas.0511326103. Epub 2006 Feb 17.
A key role for nitric oxide (NO) in penile erection is well established, but the relative roles of the neuronal NO synthase (nNOS) versus endothelial forms of NOS are not clear. nNOS- and endothelial NOS-deficient mice maintain erectile function and reproductive capacity, questioning the importance of NO. Alternatively, residual NO produced by shorter transcripts in the nNOS(-/-) animals might suffice for normal physiologic function. We show that the beta splice variant of nNOS elicits normal erection despite a decrease in stimulus-response characteristics and a 5-fold increased sensitivity to the NOS inhibitor, l-NAME. Residual nNOSbeta generates only 10% of the normal NO level in vitro but produces citrulline and diaphorase staining reflecting in vivo NOS activity in pelvic ganglion nerves that is comparable to WT animals. Thus, alternatively spliced forms of nNOS are major mediators of penile erection and so may be targets for therapeutic intervention.
一氧化氮（NO）在阴茎勃起中起关键作用已得到充分证实，但神经元型一氧化氮合酶（nNOS）与内皮型一氧化氮合酶的相对作用尚不清楚。nNOS和内皮型一氧化氮合酶缺陷的小鼠保持勃起功能和生殖能力，这对NO的重要性提出了质疑。另外，nNOS（-/-）动物中较短转录本产生的残余NO可能足以维持正常生理功能。我们发现，尽管刺激反应特性有所下降且对一氧化氮合酶抑制剂L-NAME的敏感性增加了5倍，但nNOS的β剪接变体仍能引发正常勃起。残余的nNOSβ在体外仅产生正常NO水平的10%，但能产生瓜氨酸和反映盆腔神经节神经体内一氧化氮合酶活性的黄递酶染色，这与野生型动物相当。因此，nNOS的可变剪接形式是阴茎勃起的主要介质，可能是治疗干预的靶点。
