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Publication : Cyclic AMP-dependent phosphorylation of neuronal nitric oxide synthase mediates penile erection.

First Author  Hurt KJ Year  2012
Journal  Proc Natl Acad Sci U S A Volume  109
Issue  41 Pages  16624-9
PubMed ID  23012472 Mgi Jnum  J:190323
Mgi Id  MGI:5448597 Doi  10.1073/pnas.1213790109
Citation  Hurt KJ, et al. (2012) Cyclic AMP-dependent phosphorylation of neuronal nitric oxide synthase mediates penile erection. Proc Natl Acad Sci U S A 109(41):16624-9
abstractText  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.
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