Literature DB >> 23012472

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

K Joseph Hurt1, Sena F Sezen, Gwen F Lagoda, Biljana Musicki, Gerald A Rameau, Solomon H Snyder, Arthur L Burnett.   

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.

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Year:  2012        PMID: 23012472      PMCID: PMC3478647          DOI: 10.1073/pnas.1213790109

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


  50 in total

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6.  Intracavernosal pressure monitoring in mice: responses to electrical stimulation of the cavernous nerve and to intracavernosal drug administration.

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8.  Neuronal nitric-oxide synthase mutant (Ser-1412 --> Asp) demonstrates surprising connections between heme reduction, NO complex formation, and catalysis.

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9.  Identification of regulatory sites of phosphorylation of the bovine endothelial nitric-oxide synthase at serine 617 and serine 635.

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  41 in total

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Review 7.  Gasotransmitters in pregnancy: from conception to uterine involution.

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Journal:  Biol Reprod       Date:  2019-07-01       Impact factor: 4.285

8.  cAMP-dependent post-translational modification of neuronal nitric oxide synthase neuroprotects penile erection in rats.

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10.  Chronic β1-adrenergic blockade enhances myocardial β3-adrenergic coupling with nitric oxide-cGMP signaling in a canine model of chronic volume overload: new insight into mechanisms of cardiac benefit with selective β1-blocker therapy.

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