Skip to main content
SpringerLink
Log in

Functional evidence for nitrergic neurotransmission in a human clitoral corpus cavernosum: a case study

  • Original Research
  • Published:
International Journal of Impotence Research Submit manuscript

Abstract

Although the presence of neuronal nitric oxide synthase (nNOS) has been demonstrated in human clitoral corpus cavernosum, functional evidence for the nitrergic neurotransmission as a nonadrenergic noncholinergic (NANC) transmitter has been limited to animal studies. Here we show that electrical field stimulation elicited reproducible NANC relaxation responses in a clitoral corpus cavernosum, obtained from a 38-y-old woman undergoing clitoral reduction surgery. These relaxation responses were abolished by an inhibitor of NO synthase or tetrodotoxin proving that they were nitrergic in nature and neuronal in origin. Large and small calibre nitrergic nerves were demonstrated with immunohistochemistry using nNOS antibody, which were also immunostained with cholinergic nerve markers. nNOS expression was confirmed using Western blotting. This is the first report to show that NO produced by nNOS within the cholinergic–nitrergic nerves is responsible for the NANC relaxation responses in a human clitoral corpus cavernosum.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Andersson KE . Neurophysiology/pharmacology of erection. Int J Impot Res 2001; 13: S8–S17.

    Article  Google Scholar 

  2. Ignarro LJ et al. Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem Biophys Res Commun 1990; 170: 843–850.

    Article  CAS  Google Scholar 

  3. Kim N, Azadzoi KM, Goldstein I, Saenz de Tejada I . A nitric oxide-like factor mediates nonadrenergic-noncholinergic neurogenic relaxation of penile corpus cavernosum smooth muscle. J Clin Invest 1991; 88: 112–118.

    Article  CAS  Google Scholar 

  4. Pickard RS, Powell PH, Zar MA . The effect of inhibitors of nitric oxide biosynthesis and cyclic GMP formation on nerve-evoked relaxation of human cavernosal smooth muscle. Br J Pharmacol 1991; 104: 755–759.

    Article  CAS  Google Scholar 

  5. Holmquist F, Hedlund H, Andersson KE . Characterization of inhibitory neurotransmission in the isolated corpus cavernosum from rabbit and man. J Physiol 1992; 449: 295–311.

    Article  CAS  Google Scholar 

  6. Burnett AL et al. Immunohistochemical description of nitric oxide synthase isoforms in human clitoris. J Urol 1997; 158: 75–78.

    Article  CAS  Google Scholar 

  7. Cellek S, Moncada S . Nitrergic neurotransmission mediates the non-adrenergic non-cholinergic responses in the clitoral corpus cavernosum of the rabbit. Br J Pharmacol 1998; 125: 1627–1629.

    Article  CAS  Google Scholar 

  8. Rust J, Golombok S . The Golombok-Rust inventory of sexual satisfaction (GRISS). Br J Clin Psychol 1985; 24: 63–64.

    Article  Google Scholar 

  9. Herbison AE, Simonian SX, Norris PJ, Emson PC . Relationship of neuronal nitric oxide synthase immunoreactivity to GnRH neurons in the ovariectomized and intact female rat. J Neuroendocrinol 1996; 8: 73–82.

    Article  CAS  Google Scholar 

  10. Vemulapalli S, Kurowski S . Sildenafil relaxes rabbit clitoral corpus cavernosum. Life Sci 2000; 67: 23–29.

    Article  CAS  Google Scholar 

  11. Angulo J et al. Vardenafil enhances clitoral and vaginal blood flow responses to pelvic nerve stimulation in female dogs. Int J Impot Res 2003; 15: 137–141.

    Article  CAS  Google Scholar 

  12. Ziessen T, Moncada S, Cellek S . Characterization of the non-nitrergic NANC relaxation responses in the rabbit vaginal wall. Br J Pharmacol 2002; 135: 546–554.

    Article  CAS  Google Scholar 

  13. Ziessen T, Cellek S . Purines and pyrimidines are not involved in NANC relaxant responses in the rabbit vaginal wall. Br J Pharmacol 2002; 137: 513–521.

    Article  CAS  Google Scholar 

  14. Hedlund P, Ny L, Alm P, Andersson KE . Cholinergic nerves in human corpus cavernosum and spongiosum contain nitric oxide synthase and heme oxygenase. J Urol 2000; 164: 868–875.

    Article  CAS  Google Scholar 

  15. Hedlund P, Alm P, Andersson KE . NO synthase in cholinergic nerves and NO-induced relaxation in the rat isolated corpus cavernosum. Br J Pharmacol 1999; 127: 349–360.

    Article  CAS  Google Scholar 

  16. Park K et al. Vasculogenic female sexual dysfunction: the hemodynamic basis for vaginal engorgement insufficiency and clitoral erectile insufficiency. Int J Impot Res 1997; 9: 27–37.

    Article  CAS  Google Scholar 

  17. Min K et al. Sildenafil augments pelvic nerve-mediated female genital sexual arousal in the anesthetized rabbit. Int J Impot Res 2000; 12: S32–S39.

    Article  Google Scholar 

Download references

Acknowledgements

NS Crouch is a recipient of a grant from the Elizabeth Garrett Anderson Hospital Trustees. S Cellek is a fellow of the Juvenile Diabetes Research Foundation International.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, University College London, London, UK

    S M Creighton & N S Crouch

  2. Wolfson Institute for Biomedical Research, University College London, London, UK

    N A Foxwell & S Cellek

Authors
  1. S M Creighton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N S Crouch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N A Foxwell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Cellek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S Cellek.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Creighton, S., Crouch, N., Foxwell, N. et al. Functional evidence for nitrergic neurotransmission in a human clitoral corpus cavernosum: a case study. Int J Impot Res 16, 319–324 (2004). https://doi.org/10.1038/sj.ijir.3901162

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijir.3901162

  • Springer Nature Limited

Keywords

Search

Navigation