Alternatively spliced neuronal nitric oxide synthase mediates penile erection.
A key role for nitric oxide (NO) in penile erection is well established, but the relative roles of the neuronal NO synthase (nNOS) versus endothelial forms of NOS are not clear. nNOS- and endothelial NOS-deficient mice maintain erectile function and reproductive capacity, questioning the importance of NO. Alternatively, residual NO produced by shorter transcripts in the nNOS(-/-) animals might suffice for normal physiologic function. We show that the beta splice variant of nNOS elicits normal erection despite a decrease in stimulus-response characteristics and a 5-fold increased sensitivity to the NOS inhibitor, l-NAME. Residual nNOSbeta generates only 10% of the normal NO level in vitro but produces citrulline and diaphorase staining reflecting in vivo NOS activity in pelvic ganglion nerves that is comparable to WT animals. Thus, alternatively spliced forms of nNOS are major mediators of penile erection and so may be targets for therapeutic intervention.
Department of Urology, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
K Joseph
KJ
Hurt
Sena F
SF
Sezen
Hunter C
HC
Champion
Julie K
JK
Crone
Michael A
MA
Palese
Paul L
PL
Huang
Akira
A
Sawa
Xiaojiang
X
Luo
Biljana
B
Musicki
Solomon H
SH
Snyder
Arthur L
AL
Burnett
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D004558:Electric Stimulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000201:enzymology; D052248:Nitric Oxide Synthase Type I / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D010410:Penile Erection / Q000502:physiology*; D010413:Penis / Q000201:enzymology* / Q000502:physiology*
D052248:Nitric Oxide Synthase Type I