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. 1993 Jun;34(6):814–817. doi: 10.1136/gut.34.6.814

Relaxation of distal colonic circular smooth muscle by nitric oxide derived from human leucocytes.

S J Middleton 1, M Shorthouse 1, J O Hunter 1
PMCID: PMC1374268  PMID: 8314515

Abstract

The role of nitric oxide (NO) as a mediator of colonic circular smooth muscle relaxation by human leucocytes was investigated. Granulocytes and mononuclear cells were obtained by gradient centrifugation of venous blood from healthy volunteers. Both cell types relaxed precontracted distal colonic circular smooth muscle in a concentration dependent manner. Muscle relaxation was inhibited by preincubation of cells with NG-monomethyl-L-arginine (100 microM/l) but not by preincubation with NG-monomethyl-D-arginine (100 microM/l). Muscle relaxation by cells was reduced by 200 nM oxyhaemoglobin and 10 microM methylene blue but was increased by 60 units/ml superoxide dismutase. Non-viable cells did not produce muscle relaxation. Activation of mononuclear cells by incubation with 100 nM/l FMet-Leu-Phe increased muscle relaxation, whereas activation of granulocytes did not. Granulocytes and mononuclear cells relax precontracted distal colonic circular smooth muscle in vitro by the release of NO that may contribute to motility disorders of the gut associated with inflammation.

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Selected References

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

  1. Arnold W. P., Mittal C. K., Katsuki S., Murad F. Nitric oxide activates guanylate cyclase and increases guanosine 3':5'-cyclic monophosphate levels in various tissue preparations. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3203–3207. doi: 10.1073/pnas.74.8.3203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. CONNELL A. M. The motility of the pelvic colon. II. Paradoxical motility in diarrhoea and constipation. Gut. 1962 Dec;3:342–348. doi: 10.1136/gut.3.4.342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Garrett J. M., Sauer W. G., Moertel C. G. Colonic motility in ulcerative colitis after opiate administration. Gastroenterology. 1967 Jul;53(1):93–100. [PubMed] [Google Scholar]
  5. Gryglewski R. J., Palmer R. M., Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature. 1986 Apr 3;320(6061):454–456. doi: 10.1038/320454a0. [DOI] [PubMed] [Google Scholar]
  6. Heppell J., Farkouh E., Dubé S., Péloquin A., Morgan S., Bernard D. Toxic megacolon. An analysis of 70 cases. Dis Colon Rectum. 1986 Dec;29(12):789–792. doi: 10.1007/BF02555345. [DOI] [PubMed] [Google Scholar]
  7. Ignarro L. J., Harbison R. G., Wood K. S., Kadowitz P. J. Activation of purified soluble guanylate cyclase by endothelium-derived relaxing factor from intrapulmonary artery and vein: stimulation by acetylcholine, bradykinin and arachidonic acid. J Pharmacol Exp Ther. 1986 Jun;237(3):893–900. [PubMed] [Google Scholar]
  8. Ignarro L. J. Nitric oxide. A novel signal transduction mechanism for transcellular communication. Hypertension. 1990 Nov;16(5):477–483. doi: 10.1161/01.hyp.16.5.477. [DOI] [PubMed] [Google Scholar]
  9. Ito Y., Kitamura K., Kuriyama H. Actions of nitroglycerine on the membrane and mechanical properties of smooth muscles of the coronary artery of the pig. Br J Pharmacol. 1980 Oct;70(2):197–204. doi: 10.1111/j.1476-5381.1980.tb07925.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Iyengar R., Stuehr D. J., Marletta M. A. Macrophage synthesis of nitrite, nitrate, and N-nitrosamines: precursors and role of the respiratory burst. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6369–6373. doi: 10.1073/pnas.84.18.6369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. KERN F., Jr, ALMY T. P., ABBOT F. K., BOGDONOFF M. D. The motility of the distal colon in nonspecific ulcerative colitis. Gastroenterology. 1951 Nov;19(3):492–503. [PubMed] [Google Scholar]
  12. Marletta M. A., Yoon P. S., Iyengar R., Leaf C. D., Wishnok J. S. Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry. 1988 Nov 29;27(24):8706–8711. doi: 10.1021/bi00424a003. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. McCall T. B., Boughton-Smith N. K., Palmer R. M., Whittle B. J., Moncada S. Synthesis of nitric oxide from L-arginine by neutrophils. Release and interaction with superoxide anion. Biochem J. 1989 Jul 1;261(1):293–296. doi: 10.1042/bj2610293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McCall T., Vallance P. Nitric oxide takes centre-stage with newly defined roles. Trends Pharmacol Sci. 1992 Jan;13(1):1–6. doi: 10.1016/0165-6147(92)90002-n. [DOI] [PubMed] [Google Scholar]
  16. Nakatsu K., Diamond J. Role of cGMP in relaxation of vascular and other smooth muscle. Can J Physiol Pharmacol. 1989 Apr;67(4):251–262. doi: 10.1139/y89-042. [DOI] [PubMed] [Google Scholar]
  17. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  18. Rees D. D., Palmer R. M., Hodson H. F., Moncada S. A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation. Br J Pharmacol. 1989 Feb;96(2):418–424. doi: 10.1111/j.1476-5381.1989.tb11833.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. SPRIGGS E. A., CODE C. F., BARGEN J. A., CURTISS R. K., HIGHTOWER N. C., Jr Motility of the pelvic colon and rectum of normal persons and patients with ulcerative colitis. Gastroenterology. 1951 Nov;19(3):480–491. [PubMed] [Google Scholar]
  20. 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]
  21. Sanders K. M., Stevens R., Burke E., Ward S. W. Slow waves actively propagate at submucosal surface of circular layer in canine colon. Am J Physiol. 1990 Aug;259(2 Pt 1):G258–G263. doi: 10.1152/ajpgi.1990.259.2.G258. [DOI] [PubMed] [Google Scholar]
  22. Schmidt H. H., Seifert R., Böhme E. Formation and release of nitric oxide from human neutrophils and HL-60 cells induced by a chemotactic peptide, platelet activating factor and leukotriene B4. FEBS Lett. 1989 Feb 27;244(2):357–360. doi: 10.1016/0014-5793(89)80562-9. [DOI] [PubMed] [Google Scholar]
  23. Smith T. K., Reed J. B., Sanders K. M. Interaction of two electrical pacemakers in muscularis of canine proximal colon. Am J Physiol. 1987 Mar;252(3 Pt 1):C290–C299. doi: 10.1152/ajpcell.1987.252.3.C290. [DOI] [PubMed] [Google Scholar]
  24. Snape W. J., Jr, Kao H. W. Role of inflammatory mediators in colonic smooth muscle function in ulcerative colitis. Dig Dis Sci. 1988 Mar;33(3 Suppl):65S–70S. doi: 10.1007/BF01538133. [DOI] [PubMed] [Google Scholar]
  25. Snape W. J., Jr, Matarazzo S. A., Cohen S. Abnormal gastrocolonic response in patients with ulcerative colitis. Gut. 1980 May;21(5):392–396. doi: 10.1136/gut.21.5.392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Stamler J. S., Simon D. I., Osborne J. A., Mullins M. E., Jaraki O., Michel T., Singel D. J., Loscalzo J. S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):444–448. doi: 10.1073/pnas.89.1.444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Stuehr D. J., Gross S. S., Sakuma I., Levi R., Nathan C. F. Activated murine macrophages secrete a metabolite of arginine with the bioactivity of endothelium-derived relaxing factor and the chemical reactivity of nitric oxide. J Exp Med. 1989 Mar 1;169(3):1011–1020. doi: 10.1084/jem.169.3.1011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. TRUELOVE S. C., WITTS L. J. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J. 1955 Oct 29;2(4947):1041–1048. doi: 10.1136/bmj.2.4947.1041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Wright C. D., Mülsch A., Busse R., Osswald H. Generation of nitric oxide by human neutrophils. Biochem Biophys Res Commun. 1989 Apr 28;160(2):813–819. doi: 10.1016/0006-291x(89)92506-0. [DOI] [PubMed] [Google Scholar]

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