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

K. Joseph Hurt, Sena F. Sezen, Gwen F. Lagoda, Biljana Musicki, Gerald A. Rameau, Solomon H. Snyder, Arthur L. Burnett

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)16624-16629
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number41
StatePublished - Oct 9 2012


  • Cyclic GMP
  • Endothelial NOS
  • Gasotransmitter
  • Phosphoantibody
  • Smooth muscle relaxation

ASJC Scopus subject areas

  • General


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