Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16624-9. doi: 10.1073/pnas.1213790109. Epub 2012 Sep 24.
Nitric oxide (NO) generated by neuronal NO synthase (nNOS) initiates penile erection, but has not been thought to participate in the sustained erection required for normal sexual performance. We now show that cAMP-dependent phosphorylation of nNOS mediates erectile physiology, including sustained erection. nNOS is phosphorylated by cAMP-dependent protein kinase (PKA) at serine(S)1412. Electrical stimulation of the penile innervation increases S1412 phosphorylation that is blocked by PKA inhibitors but not by PI3-kinase/Akt inhibitors. Stimulation of cAMP formation by forskolin also activates nNOS phosphorylation. Sustained penile erection elicited by either intracavernous forskolin injection, or augmented by forskolin during cavernous nerve electrical stimulation, is prevented by the NOS inhibitor L-NAME or in nNOS-deleted mice. Thus, nNOS mediates both initiation and maintenance of penile erection, implying unique approaches for treating erectile dysfunction.
神经元型一氧化氮合酶（nNOS）产生的一氧化氮（NO）引发阴茎勃起，但人们一直认为它不会参与正常性行为所需的持续勃起。我们现在表明，cAMP 依赖性蛋白激酶（PKA）对 nNOS 的磷酸化介导了包括持续勃起在内的勃起生理过程。nNOS 在丝氨酸（S）1412 被 cAMP 依赖性蛋白激酶（PKA）磷酸化。阴茎神经支配的电刺激增加 S1412 磷酸化，该磷酸化被 PKA 抑制剂阻断，但不受 PI3-激酶/Akt 抑制剂阻断。 forskolin 形成 cAMP 的刺激也激活 nNOS 磷酸化。无论是通过腔内注射 forskolin 还是通过在海绵体神经电刺激期间增加 forskolin 来引发持续的阴茎勃起，都可以被 NOS 抑制剂 L-NAME 或 nNOS 缺失的小鼠所预防。因此，nNOS 介导阴茎勃起的启动和维持，暗示着治疗勃起功能障碍的独特方法。
