Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection
| Autor: | John L. Moriarity, Arthur L. Burnett, Solomon H. Snyder, Julie K. Crone, K. Joseph Hurt, Michael Palese, Biljana Musicki, Robyn E. Becker |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Nitric Oxide Synthase Type III Morpholines Nitric Oxide Synthase Type I Protein Serine-Threonine Kinases Endothelial NOS Nitric Oxide Models Biological Nitric oxide Wortmannin Rats Sprague-Dawley chemistry.chemical_compound Phosphatidylinositol 3-Kinases Enos Internal medicine Papaverine Proto-Oncogene Proteins medicine Animals Endothelium Phosphorylation Protein kinase B PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors Multidisciplinary biology Penile Erection Biological Sciences biology.organism_classification Electric Stimulation Rats Androstadienes Enzyme Activation Endocrinology chemistry Chromones Nitric Oxide Synthase Proto-Oncogene Proteins c-akt medicine.drug Penis |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 99(6) |
| ISSN: | 0027-8424 |
| Popis: | 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 (PI3kinase)/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. |
| Databáze: | OpenAIRE |
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