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.
Written by:
Hurt KJ, Sezen SF, Lagoda GF, Musicki B, Rameau GA, Snyder SH, Burnett AL. Are you the author?
Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Reference: Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16624-9
doi: 10.1073/pnas.1213790109
PubMed Abstract
PMID: 23012472
