Alternatively spliced neuronal nitric oxide synthase mediates penile erection


HURT K. , Sezen S., CHAMPION H., CRONE J., PALESE M., HUANG P., ...More

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol.103, no.9, pp.3440-3443, 2006 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 103 Issue: 9
  • Publication Date: 2006
  • Doi Number: 10.1073/pnas.0511326103
  • Title of Journal : PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
  • Page Numbers: pp.3440-3443

Abstract

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 nNOS beta 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.