The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection
Open accessAbstract
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.
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Citations
Cites
Nitric oxide and the immune response
Bogdan, C. (2001) · Nature Immunology · doi:10.1038/ni1001-907 · Cited by 3,447
Hypertension in mice lacking the gene for endothelial nitric oxide synthase
Huang, P. L., Huang, Z., Mashimo, H., Bloch, K. D., Moskowitz, M. A., Bevan, J. A., & Fishman, M. C. (1995) · Nature · doi:10.1038/377239a0 · Cited by 2,070
Du, X. L., Edelstein, D., Dimmeler, S., Ju, Q., Sui, C., & Brownlee, M. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11235 · Cited by 907
Cited by
Chapter 2 PI3K/PTEN Signaling in Angiogenesis and Tumorigenesis
(2009) · Advances in Cancer Research · doi:10.1016/s0065-230x(09)02002-8 · Cited by 620
Tadalafil in the treatment of erectile dysfunction
Coward, R., & Carson, C. (2008) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s3336 · Cited by 138
Musicki, B., Liu, T., Strong, T., Jin, L., Laughlin, M. H., Turk, J. R., & Burnett, A. L. (2008) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2007.00731.x · Cited by 58
Self-citation(2005) · doi:10.1111/j.1743-6109.2005.00098_1.x · Cited by 31
El Taieb, M., Hegazy, E., & Ibrahim, A. (2019) · The Journal of Sexual Medicine · doi:10.1016/j.jsxm.2019.06.009 · Cited by 22
Metadata
- Authors
- Hurt, K. J., Musicki, B., Palese, M. A., Crone, J. K., Becker, R. E., Moriarity, J. L., Snyder, S. H., & Burnett, A. L.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2002-03-19
- Volume
- 99
- Issue
- 6
- Pages
- 4061-4066
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2152357927
- Cited by
- 379
- References
- 3
- FWCI
- 10.50
- Type
- journal article
- Language
- en
- Open access
- bronze
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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