Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection

K. Joseph Hurt, Biljana Musicki, Michael A. Palese, Julie K. Crone, Robyn E. Becker, John L. Moriarity, Solomon H Snyder, Arthur Burnett

Research output: Contribution to journalArticle

Abstract

In the penis, nitric oxide (NO) can be formed by both neuronal NO synthase and endothelial NOS (eNOS). eNOS is activated by viscous drag/shear stress in blood vessels to produce NO continuously, a process mediated by the phosphatidylinositol 3-kinase (PI3-kinase)/Akt pathway. Here we show that PI3-kinase/Akt physiologically mediates erection. Both electrical stimulation of the cavernous nerve and direct intracavernosal injection of the vasorelaxant drug papaverine cause rapid increases in phosphorylated (activated) Akt and eNOS. Phosphorylation is diminished by wortmannin and LY294002, inhibitors of PI3-kinase, the upstream activator of Akt. The two drugs also reduce erection. Penile erection elicited by papaverine is reduced profoundly in mice with targeted deletion of eNOS. Our findings support a model in which rapid, brief activation of neuronal NOS initiates the erectile process, whereas PI3-kinase/Akt-dependent phosphorylation and activation of eNOS leads to sustained NO production and maximal erection.

Original languageEnglish (US)
Pages (from-to)4061-4066
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number6
DOIs
StatePublished - Mar 19 2002

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Phosphatidylinositol 3-Kinase
Penile Erection
Nitric Oxide Synthase Type III
Phosphorylation
Papaverine
Nitric Oxide
Nitric Oxide Synthase Type I
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Penis
Vasodilator Agents
Pharmaceutical Preparations
Electric Stimulation
Blood Vessels
Injections

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection. / Hurt, K. Joseph; Musicki, Biljana; Palese, Michael A.; Crone, Julie K.; Becker, Robyn E.; Moriarity, John L.; Snyder, Solomon H; Burnett, Arthur.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 6, 19.03.2002, p. 4061-4066.

Research output: Contribution to journalArticle

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AU - Musicki, Biljana

AU - Palese, Michael A.

AU - Crone, Julie K.

AU - Becker, Robyn E.

AU - Moriarity, John L.

AU - Snyder, Solomon H

AU - Burnett, Arthur

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AB - In the penis, nitric oxide (NO) can be formed by both neuronal NO synthase and endothelial NOS (eNOS). eNOS is activated by viscous drag/shear stress in blood vessels to produce NO continuously, a process mediated by the phosphatidylinositol 3-kinase (PI3-kinase)/Akt pathway. Here we show that PI3-kinase/Akt physiologically mediates erection. Both electrical stimulation of the cavernous nerve and direct intracavernosal injection of the vasorelaxant drug papaverine cause rapid increases in phosphorylated (activated) Akt and eNOS. Phosphorylation is diminished by wortmannin and LY294002, inhibitors of PI3-kinase, the upstream activator of Akt. The two drugs also reduce erection. Penile erection elicited by papaverine is reduced profoundly in mice with targeted deletion of eNOS. Our findings support a model in which rapid, brief activation of neuronal NOS initiates the erectile process, whereas PI3-kinase/Akt-dependent phosphorylation and activation of eNOS leads to sustained NO production and maximal erection.

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