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Let's make NO mistake!

International Journal of Impotence Research volume 17, pages 388–389 (2005)Cite this article

Several publications or presentations in the field of sexual medicine have used erroneous terminology and methodology about nitric oxide (NO). Although these have been pointed out in the meetings or during the manuscript review processes, the corrections remained anecdotal and no written commentary can be found to lead young scientists in the field. Since one of the main aims of the International Journal of Impotence Research (IJIR) is education, I would like to draw the attention of readers to these mistakes:

NO is now known to be the one of the major mediators of penile erection and clitoral tumescence. We know that there are two main sources of NO in the penis and clitoris: the endothelium and nerves. These NO-producing nerves have frequently and erroneously been described as ‘NANC nerves’. I would like to try to explain here what NANC means and why ‘NANC nerve’ is the wrong terminology: Nonadrenergic noncholinergic (NANC) neurotransmission was first described in late 19th century when atropine-resistant excitation of the bladder was demonstrated in response to pelvic nerve stimulation,1 and relaxation of the stomach during vagal nerve stimulation was revealed following atropine treatment.2 NANC neurotransmission leading to relaxation of the urogenital smooth muscle was first described by Gillespie in the early 1970s.3 He showed that stimulation of intrinsic nerves in the anococcygeus and retractor penis muscles caused contraction, which could be blocked with tetrodotoxin (a nerve-blocking agent), guanethidine (an inhibitor of noradrenaline release) or alpha-1 adrenoceptor antagonists (inhibiting the effect of noradrenaline on the smooth muscle), suggesting that these contractions are mediated by neuronal release of noradrenaline. After blockade of noradrenergic contractions and elevation of the tone of the tissue, the same stimulation caused relaxation. These relaxations were not affected by either alpha-receptor or muscarinic-receptor antagonists, suggesting the existence of a NANC inhibitory neurotransmitter. In subsequent years, many endogenous substances such as vasoactive intestinal peptide and adenosine triphosphate have been suggested to be this NANC neurotransmitter. However, they did not convincingly mimic the inhibitory NANC response. In the late 1980s, similarities between endothelium-derived relaxing factor (EDRF) and the inhibitory NANC transmitter were observed. The discovery that EDRF was NO provided the evidence required for the later identification of the inhibitory NANC transmitter as NO. Today we know that NO is released as an NANC neurotransmitter in the penis and clitoris as well as many other smooth muscle structures in the body, ranging from blood vessels to the gastrointestinal tract. The term NANC therefore refers to the type of neurotransmission, not to the type of nerve. NO is an NANC neurotransmitter; however, it is released from different subsets of nerves in different tissues. In the penis and clitoris, it is now widely accepted that NO is released from postganglionic parasympathetic (cholinergic) nerves.4 Therefore, although it may sound ironic, NO is an NANC transmitter, which is released from cholinergic nerves in the penis and clitoris. ‘Nitrergic nerve’5 or ‘NO-releasing/producing autonomic nerve’ are more suitable terms than ‘NANC nerve’ for NO-releasing nerves in the penis and clitoris.

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References

  1. Langley JN, Anderson HK . The innervation of pelvic and adjoining viscera-IV. Intern Generative Organs 1885; 19: 122–130.

    Google Scholar 

  2. Langley JN . On inhibitory fibres in the vagus for the end of the oesofagus and stomach. J Physiol 1898; 23: 407–414.

    Article  CAS  Google Scholar 

  3. Gillespie JS . The rat anococcygeus muscle and its response to nerve stimulation and to some drugs. Br J Pharmacol 1972; 45: 404–416.

    Article  CAS  Google Scholar 

  4. 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 

  5. Moncada S, Higgs A, Furchgott R . International Union of Pharmacology Nomenclature in Nitric Oxide Research. Pharmacol Rev 1997; 49: 137–142.

    CAS  PubMed  Google Scholar 

  6. Alexander SPH, Mathie A, Peters JA . Guide to receptors and channels. Br J Pharmacol 2004; 141: S115.

    Google Scholar 

  7. Moore PK, Handy RL . Selective inhibitors of neuronal nitric oxide synthase—is no NOS really good NOS for the nervous system? Trends Pharmacol Sci 1997; 18: 204–211.

    CAS  PubMed  Google Scholar 

  8. Knowles RG, Salter M . Measurement of NOS activity by conversion of radiolabeled arginine to citrulline using ion-exchange separation. In: Titheradge MA (ed). Nitric Oxide Protocols. Humana Press: Totowa, 1998, pp 67–73.

    Google Scholar 

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  1. S Cellek

    Present address: Neurology-GI CEDD, GlaxoSmithKline, New Frontiers Science Park North, Third Avenue, Harlow, Essex, CM19 5AW, UK

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

    S Cellek

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Cellek, S. Let's make NO mistake!. Int J Impot Res 17, 388–389 (2005). https://doi.org/10.1038/sj.ijir.3901315

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