title: Cyclic AMP-dependent phosphorylation of neuronal nitric oxide synthase mediates penile erection.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: K Joseph
authors.initials: KJ
authors.lastname: Hurt
authors.forename: Sena F
authors.initials: SF
authors.lastname: Sezen
authors.forename: Gwen F
authors.initials: GF
authors.lastname: Lagoda
authors.forename: Biljana
authors.initials: B
authors.lastname: Musicki
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Rameau
authors.forename: Solomon H
authors.initials: SH
authors.lastname: Snyder
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Burnett
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010410:Penile Erection / Q000187:drug effects / Q000502:physiology*; D010413:Penis / Q000294:innervation / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D005576:Colforsin; D012694:Serine; D000242:Cyclic AMP; D052248:Nitric Oxide Synthase Type I; D017868:Cyclic AMP-Dependent Protein Kinases; D019331:NG-Nitroarginine Methyl Ester