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

Proceedings of the National Academy of Sciences of the United States of America
K Joseph HurtArthur L Burnett

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 (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.

References

Jul 17, 1992·Science·A L BurnettS H Snyder
Mar 1, 1992·Biology of Reproduction·T M MillsV S Stopper
Jan 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·D S Bredt, S H Snyder
Dec 1, 1983·The Journal of Urology·T F LueE A Tanagho
Jun 1, 1994·The Journal of Urology·W J HellstromJ A Roberts
Jun 1, 1993·The Journal of Urology·A C Campos de CarvalhoD C Spray
Feb 1, 1993·The American Journal of Physiology·S L Andersen, T Clausen
Oct 1, 1995·Cell and Tissue Research·W G DailR Galindo
Jan 1, 1997·The Journal of Urology·A L Burnett
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·M J EliassonS H Snyder
Mar 6, 1999·The Journal of Physiology·A EscrigM Mas
Sep 2, 1999·Current Biology : CB·B J MichellR B Pearson
Feb 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·P HedlundK E Andersson
Feb 26, 2000·Acta Physiologica Scandinavica·B FisslthalerI Fleming
Jul 29, 2000·European Journal of Endocrinology·M MaggiG Forti
Sep 29, 2001·Nature Immunology·C Bogdan
Oct 13, 2001·Diabetologia·L De AngelisD Giugliano
Jan 10, 2002·Journal of Andrology·Arthur L BurnettSena E Sezen

❮ Previous
Next ❯

Citations

Aug 25, 2005·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Yan TanJizhou Xiang
Oct 21, 2006·Current Urology Reports·Trinity J Bivalacqua, Arthur L Burnett
Mar 5, 2004·Nitric Oxide : Biology and Chemistry·Matthew R NangleNorman E Cameron
May 4, 2005·Pharmacology & Therapeutics·Noboru TodaTomio Okamura
Jul 25, 2003·European Journal of Pharmacology·Naomi HosogaiSeitaro Mutoh
Jun 6, 2009·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Kazuhide AyajikiNoboru Toda
Nov 13, 2008·International Journal of Impotence Research·F Giuliano
Feb 4, 2011·International Journal of Impotence Research·J M JohnsonB Musicki
Oct 7, 2011·International Journal of Impotence Research·X Jiang, K Chitaley
Oct 5, 2012·International Journal of Impotence Research·H NingC-S Lin
Apr 19, 2013·International Journal of Impotence Research·A SubramoniamB K Arun
Apr 26, 2007·Nature Clinical Practice. Cardiovascular Medicine·Gerald F WattsBronwyn G A Stuckey
Mar 11, 2006·International Journal of Impotence Research·P J Mateos-CáceresA J López-Farré
Jun 16, 2006·International Journal of Impotence Research·B Musicki, A L Burnett
Aug 25, 2007·International Journal of Impotence Research·A F BradingH Hashitani
Jul 20, 2007·International Journal of Impotence Research·D Prieto
Dec 7, 2007·International Journal of Impotence Research·S NimmegeersJ Van de Voorde
Feb 8, 2008·International Journal of Impotence Research·T D StrongT J Bivalacqua
Sep 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·K Joseph HurtArthur L Burnett
Nov 29, 2008·Cardiovascular Research·Fulvio MorelloEmilio Hirsch
May 14, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jiaming WenYang Xia
May 9, 2006·Journal of Cardiovascular Pharmacology·Alexis ZambleFrançoise Martin-Nizard
Jan 11, 2005·British Journal of Haematology·Vikki G NolanMartin H Steinberg
Sep 24, 2011·The Journal of Pharmacology and Experimental Therapeutics·Elizabeth A TownsendY S Prakash
Apr 30, 2009·Science Signaling·Asif K MustafaSolomon H Snyder
Oct 7, 2003·Annual Review of Neuroscience·Darren Boehning, Solomon H Snyder
Feb 10, 2012·PloS One·Roberta d'Emmanuele di Villa BiancaRaffaella Sorrentino
Dec 6, 2011·Asian Journal of Andrology·Mikkel FodeJens Sønksen
Dec 19, 2007·Asian Journal of Andrology·Travis D StrongTrinity J Bivalacqua
Aug 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Biljana MusickiArthur L Burnett
Jan 26, 2005·Proceedings of the National Academy of Sciences of the United States of America·Hunter C ChampionArthur L Burnett
Feb 21, 2006·Proceedings of the National Academy of Sciences of the United States of America·K Joseph HurtArthur L Burnett
Apr 17, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jorge D BrioniJames P Sullivan
Jun 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Trinity J BivalacquaPhilip J Kadowitz

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.