Open AccessCyclic AMP-dependent phosphorylation of neuronal nitric oxide synthase mediates penile erection
Author(s) -
K. Joseph Hurt,
Sena F. Sezen,
Gwen F. Lagoda,
Biljana Musicki,
Gerald A. Rameau,
Solomon H. Snyder,
Arthur L. Burnett
Publication year - 2012
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1213790109
Subject(s) - forskolin , phosphorylation , stimulation , nitric oxide synthase , erectile dysfunction , protein kinase a , endocrinology , nitric oxide , medicine , kinase , biology , chemistry , microbiology and biotechnology
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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