Skip to main content
NCBI home page
Gut logoLink to Gut
. 1993 May;34(5):689–693. doi: 10.1136/gut.34.5.689

Nerve mediated relaxation of the human internal anal sphincter: the role of nitric oxide.

T O'Kelly 1, A Brading 1, N Mortensen 1
PMCID: PMC1374191  PMID: 7684992

Abstract

The aim of this study was to determine if nitric oxide (NO) is the non-adrenergic, non-cholinergic neurotransmitter, released by enteric inhibitory nerves, which mediates relaxation of the human internal anal sphincter. Isolated muscle strips were mounted for isometric tension recording in superfusion organ baths. Sodium nitroprusside, an exogenous donor of NO, relaxed the strips in a concentration dependent manner. In the presence of atropine and guanethidine, transmural field stimulation produced tetrodotoxin sensitive relaxations, which were inhibited in a dose dependent and enantiomer specific manner by antagonists of NO synthase; completely by L-nitroarginine and partially by L-N-monomethyl arginine. The effect of these antagonists was reversed by L-arginine but not D-arginine. Oxyhaemoglobin, a scavenger of nitric oxide, also abolished the relaxations but methaemoglobin had no such effect. These results strongly suggest that NO is, or is very closely associated with, the non-adrenergic, non-cholinergic neurotransmitter mediating neurogenic relaxation of the human internal anal sphincter.

Full text

PDF
689

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Boeckxstaens G. E., Pelckmans P. A., Bogers J. J., Bult H., De Man J. G., Oosterbosch L., Herman A. G., Van Maercke Y. M. Release of nitric oxide upon stimulation of nonadrenergic noncholinergic nerves in the rat gastric fundus. J Pharmacol Exp Ther. 1991 Feb;256(2):441–447. [PubMed] [Google Scholar]
  2. Boeckxstaens G. E., Pelckmans P. A., Bult H., De Man J. G., Herman A. G., Van Maercke Y. M. Non-adrenergic non-cholinergic relaxation mediated by nitric oxide in the canine ileocolonic junction. Eur J Pharmacol. 1990 Nov 6;190(1-2):239–246. doi: 10.1016/0014-2999(90)94132-h. [DOI] [PubMed] [Google Scholar]
  3. Bredt D. S., Hwang P. M., Snyder S. H. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature. 1990 Oct 25;347(6295):768–770. doi: 10.1038/347768a0. [DOI] [PubMed] [Google Scholar]
  4. Burleigh D. E., D'Mello A., Parks A. G. Responses of isolated human internal anal sphincter to drugs and electrical field stimulation. Gastroenterology. 1979 Sep;77(3):484–490. [PubMed] [Google Scholar]
  5. Burleigh D. E. Ng-nitro-L-arginine reduces nonadrenergic, noncholinergic relaxations of human gut. Gastroenterology. 1992 Feb;102(2):679–683. doi: 10.1016/0016-5085(92)90120-n. [DOI] [PubMed] [Google Scholar]
  6. Burleigh D. E. Non-cholinergic, non-adrenergic inhibitory neurons in human internal anal sphincter muscle. J Pharm Pharmacol. 1983 Apr;35(4):258–260. doi: 10.1111/j.2042-7158.1983.tb02927.x. [DOI] [PubMed] [Google Scholar]
  7. CALLAGHAN R. P., NIXON H. H. MEGARECTUM: PHYSIOLOGICAL OBSERVATIONS. Arch Dis Child. 1964 Apr;39:153–157. doi: 10.1136/adc.39.204.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dalziel H. H., Thornbury K. D., Ward S. M., Sanders K. M. Involvement of nitric oxide synthetic pathway in inhibitory junction potentials in canine proximal colon. Am J Physiol. 1991 May;260(5 Pt 1):G789–G792. doi: 10.1152/ajpgi.1991.260.5.G789. [DOI] [PubMed] [Google Scholar]
  9. Desai K. M., Sessa W. C., Vane J. R. Involvement of nitric oxide in the reflex relaxation of the stomach to accommodate food or fluid. Nature. 1991 Jun 6;351(6326):477–479. doi: 10.1038/351477a0. [DOI] [PubMed] [Google Scholar]
  10. Feelisch M., Noack E. A. Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase. Eur J Pharmacol. 1987 Jul 2;139(1):19–30. doi: 10.1016/0014-2999(87)90493-6. [DOI] [PubMed] [Google Scholar]
  11. Garrett J. R., Howard E. R., Jones W. The internal anal sphincter in the cat: a study of nervous mechanisms affecting tone and reflex activity. J Physiol. 1974 Nov;243(1):153–166. doi: 10.1113/jphysiol.1974.sp010747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Huizinga J. D., Tomlinson J., Pintin-Quezada J. Involvement of nitric oxide in nerve-mediated inhibition and action of vasoactive intestinal peptide in colonic smooth muscle. J Pharmacol Exp Ther. 1992 Feb;260(2):803–808. [PubMed] [Google Scholar]
  13. Lubowski D. Z., Nicholls R. J., Swash M., Jordan M. J. Neural control of internal anal sphincter function. Br J Surg. 1987 Aug;74(8):668–670. doi: 10.1002/bjs.1800740804. [DOI] [PubMed] [Google Scholar]
  14. Maggi C. A., Barbanti G., Turini D., Giuliani S. Effect of NG-monomethyl L-arginine (L-NMMA) and NG-nitro L-arginine (L-NOARG) on non-adrenergic non-cholinergic relaxation in the circular muscle of the human ileum. Br J Pharmacol. 1991 Aug;103(4):1970–1972. doi: 10.1111/j.1476-5381.1991.tb12361.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Martin W., Smith J. A., White D. G. The mechanisms by which haemoglobin inhibits the relaxation of rabbit aorta induced by nitrovasodilators, nitric oxide, or bovine retractor penis inhibitory factor. Br J Pharmacol. 1986 Nov;89(3):563–571. doi: 10.1111/j.1476-5381.1986.tb11157.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  17. Murray J., Du C., Ledlow A., Bates J. N., Conklin J. L. Nitric oxide: mediator of nonadrenergic noncholinergic responses of opossum esophageal muscle. Am J Physiol. 1991 Sep;261(3 Pt 1):G401–G406. doi: 10.1152/ajpgi.1991.261.3.G401. [DOI] [PubMed] [Google Scholar]
  18. Rattan S., Chakder S. Role of nitric oxide as a mediator of internal anal sphincter relaxation. Am J Physiol. 1992 Jan;262(1 Pt 1):G107–G112. doi: 10.1152/ajpgi.1992.262.1.G107. [DOI] [PubMed] [Google Scholar]
  19. Rattan S., Sarkar A., Chakder S. Nitric oxide pathway in rectoanal inhibitory reflex of opossum internal anal sphincter. Gastroenterology. 1992 Jul;103(1):43–50. doi: 10.1016/0016-5085(92)91093-j. [DOI] [PubMed] [Google Scholar]
  20. Salvemini D., Radziszewski W., Korbut R., Vane J. The use of oxyhaemoglobin to explore the events underlying inhibition of platelet aggregation induced by NO or NO-donors. Br J Pharmacol. 1990 Dec;101(4):991–995. doi: 10.1111/j.1476-5381.1990.tb14194.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Salvemini D., de Nucci G., Gryglewski R. J., Vane J. R. Human neutrophils and mononuclear cells inhibit platelet aggregation by releasing a nitric oxide-like factor. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6328–6332. doi: 10.1073/pnas.86.16.6328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sanders K. M., Ward S. M. Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission. Am J Physiol. 1992 Mar;262(3 Pt 1):G379–G392. doi: 10.1152/ajpgi.1992.262.3.G379. [DOI] [PubMed] [Google Scholar]
  23. Speakman C. T., Kamm M. A. The internal and sphincter--new insights into faecal incontinence. Gut. 1991 Apr;32(4):345–346. doi: 10.1136/gut.32.4.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Thornbury K. D., Ward S. M., Dalziel H. H., Carl A., Westfall D. P., Sanders K. M. Nitric oxide and nitrosocysteine mimic nonadrenergic, noncholinergic hyperpolarization in canine proximal colon. Am J Physiol. 1991 Sep;261(3 Pt 1):G553–G557. doi: 10.1152/ajpgi.1991.261.3.G553. [DOI] [PubMed] [Google Scholar]
  25. Tøttrup A., Glavind E. B., Svane D. Involvement of the L-arginine-nitric oxide pathway in internal anal sphincter relaxation. Gastroenterology. 1992 Feb;102(2):409–415. doi: 10.1016/0016-5085(92)90084-c. [DOI] [PubMed] [Google Scholar]
  26. Tøttrup A., Svane D., Forman A. Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter. Am J Physiol. 1991 Mar;260(3 Pt 1):G385–G389. doi: 10.1152/ajpgi.1991.260.3.G385. [DOI] [PubMed] [Google Scholar]
  27. Vincent S. R., Hope B. T. Neurons that say NO. Trends Neurosci. 1992 Mar;15(3):108–113. doi: 10.1016/0166-2236(92)90021-y. [DOI] [PubMed] [Google Scholar]
  28. Ward S. M., Dalziel H. H., Thornbury K. D., Westfall D. P., Sanders K. M. Nonadrenergic, noncholinergic inhibition and rebound excitation in canine colon depend on nitric oxide. Am J Physiol. 1992 Feb;262(2 Pt 1):G237–G243. doi: 10.1152/ajpgi.1992.262.2.G237. [DOI] [PubMed] [Google Scholar]
  29. Ward S. M., McKeen E. S., Sanders K. M. Role of nitric oxide in non-adrenergic, non-cholinergic inhibitory junction potentials in canine ileocolonic sphincter. Br J Pharmacol. 1992 Apr;105(4):776–782. doi: 10.1111/j.1476-5381.1992.tb09056.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES