, 13:103 | Cite as

Intestinal dysmotility in inflammatory bowel disease: Mechanisms of the reduced activity of smooth muscle contraction

  • Hiroshi Ozaki
  • Masatoshi Hori
  • Kazuya Kinoshita
  • Takashi Ohama


Inflammation suppresses intestinal motility, which secondarily induces abnormal growth of intestinal flora. Disturbance of this flora plays a role in the pathogenesis of mucosal inflammation, which in turn aggravates the intestinal dysmotility. Therefore, it is important to know the mechanism of alteration in motor function in the inflamed intestine. Recent studies have shown molecular mechanisms responsible for the motility disorder in the inflamed gut. These include an increase in the activity of myosin light-chain phosphatase and an alteration of ion channel activity in smooth muscle cells.

Key words

Motility disorder inflammation gut 


  1. Akbarali, H. I., Pothoulakis, C. and Castagliuolo, I. (2000). Altered ion channel activity in murine colonic smooth muscle myocytes in an experimental colitis model, Biochem. Biophys. Res. Commun. 275, 637–642.PubMedCrossRefGoogle Scholar
  2. Al-saffar, A. and Hellstrom, P. M. (2001). Contractile responses to natural tachykinins and selective tachykinin analogs in normal and inflamed ileal and colonic muscle, Scand. J. Gastroenterol. 36, 485–493.PubMedCrossRefGoogle Scholar
  3. Annese, V., Bassotti, G., Napolitano, G., et al. (1997). Gastrointestinal motility disorders in patients with inactive crohn’s disease, Scand. J. Gastroenterol. 32, 1107–1117.PubMedCrossRefGoogle Scholar
  4. Asheroft, F. M. and Gribble, F. M. (2000). New windows on the mechanism of action of katp channel openers, Trends Pharmacol. Sci. 21, 439–445.CrossRefGoogle Scholar
  5. Bauer, A. J., Schwarz, N. T., Moore, B. A., et al. (2002). Ileus in critical illness: mechanisms and management, Curr. Opin. Crit. Care 8, 152–157.PubMedCrossRefGoogle Scholar
  6. Bossone, C., Hosseini, J. M., Pineiro-Carrero, V., et al. (2001). Alterations in spontaneous contractions in vitro after repeated inflammation of rat distal colon, Am. J. Physiol. 280, G949–G957.Google Scholar
  7. Chang, I. Y., Glasgow, N. J., Takayama, I., et al. (2001). Loss of interstitial cells of cajal and development of electrical dysfunction in murine small bowel obstruction, J. Physiol. 536, 555–568.PubMedCrossRefGoogle Scholar
  8. Collins, S. M. (1996). The immunomodulation of enteric neuromuscular function: implications for motility and inflammatory disorders, Gastroenterology 111, 1683–1699.PubMedCrossRefGoogle Scholar
  9. Depoortere, I., Thijs, T., Van Assche, G., et al. (2000). Dose-dependent effects of recombinant human interleukin-11 on contractile properties in rabbit 2,4,6-trinitrobenzene sulfonic acid colitis, J. Pharmacol. Exp. Ther. 294, 983–990.PubMedGoogle Scholar
  10. Der, T., Bercik, P., Donnelly, G., et al. (2000). Interstitial cells of cajal and inflammation-induced motor dysfunction in the mouse small intestine, Gastroenterology 119, 1590–1599.PubMedCrossRefGoogle Scholar
  11. Eto, M., Senba, S., Morita, F., et al. (1997). Molecular cloning of a novel phosphorylation-dependent inhibitory protein of protein phosphatase-1 (CPI17) in smooth muscle: its specific localization in smooth muscle, FEBS Lett. 410, 356–360.PubMedCrossRefGoogle Scholar
  12. Faussone-Pellegrini, M. S., Gay, J., Vannucchi, M. G., et al. (2002). Alterations of neurokinin receptors and interstitial cells of cajal during and after jejunal inflammation induced by nippostrongylus brasiliensis in the rat, Neurogastroenterol. Motil. 14, 83–95.PubMedCrossRefGoogle Scholar
  13. Fiocchi, C. (1998). Inflammatory bowel disease: etiology and pathogenesis, Gastroenterology 115, 182–205.PubMedCrossRefGoogle Scholar
  14. Galeazzi, F., Haapala, E. M., Van Rooijen, N., et al. (2000). Inflammation-induced impairment of enteric nerve function in nematode-infected mice is macrophage dependent, Am. J. Physiol. 278, G259–G265.Google Scholar
  15. Hamaguchi, T., Ito, M., Feng, J., et al. (2000). Phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by protein kinase N, Biochem. Biophys. Res. Commun. 274, 825–830.PubMedCrossRefGoogle Scholar
  16. Hori, M. and Karaki, H. (1998). Regulatory mechanisms of calcium sensitization of contractile elements in smooth muscle, Life Sci. 62, 1629–1633.PubMedCrossRefGoogle Scholar
  17. Hori, M., Kita, M., Torihashi, S., et al. (2001). Upregulation of inos by cox-2 in muscularis resident macrophage of rat intestine stimulated with LPS, Am. J. Physiol. 280, G930–G938.Google Scholar
  18. Hurst, S. and Collins, S. M. (1993). Interleukin-1 beta modulation of norepinephrine release from rat myenteric nerves, Am. J. Physiol. 264, G30–G35.PubMedGoogle Scholar
  19. Hurst, S. M., Stanisz, A. M., Sharkey, K. A., et al. (1993). Interleukin 1β-induced increase in substance P in rat myenteric plexus, Gastroenterology 105, 1754–1760.PubMedGoogle Scholar
  20. Jacobson, K., Mchugh, K. and Collins, S. M. (1995). Experimental colitis alters myenteric nerve function at inflamed and noninflamed sites in the rat, Gastroenterology 109, 718–722.PubMedCrossRefGoogle Scholar
  21. Jin, X., Malykhina, A. P., Lupu, F., et al. (2004). Altered gene expression and increased bursting activity of colonic smooth muscle ATP-sensitive K+ channels in experimental colitis, Am. J. Physiol. 287, G274–G285.CrossRefGoogle Scholar
  22. Kamm, K. E. and Stull, J. T. (1989). Regulation of smooth muscle contractile elements by second messengers, Annu. Rev. Physiol. 51, 299–313.PubMedCrossRefGoogle Scholar
  23. Kang, M., Morsy, N., Jin, X., et al. (2004). Protein and gene expression of Ca2+ channel isoforms in murine colon: effect of inflammation, Pflüg. Arch. 449, 288–297.Google Scholar
  24. Kinoshita, K., Sato, K., Hori, M., et al. (2003). Decrease in activity of smooth muscle 1-type Ca2+ channels and its reversal by NF-κB inhibitors in crohn’s colitis model, Am. J. Physiol. 285, G483–G493.Google Scholar
  25. Kitazawa, T., Eto, M., Woodsome, T. P., et al. (2003). Phosphorylation of the myosin phosphatase targeting subunit and CPI-17 during Ca2+ sensitization in rabbit smooth muscle, J. Physiol. 546, 879–889.PubMedCrossRefGoogle Scholar
  26. Koch, T. R., Carney, J. A., Go, V. L., et al. (1988). Spontaneous contractions and some electrophysiologic properties of circular muscle from normal sigmoid colon and ulcerative colitis, Gastroenterology 95, 77–84.PubMedGoogle Scholar
  27. Koyama, M., Ito, M., Feng, J., et al. (2000). Phosphorylation of CPI-17, an inhibitory phosphoprotein of smooth muscle myosin phosphatase, by Rho-kinase, FEBS Lett. 475, 197–200.PubMedCrossRefGoogle Scholar
  28. Liu, X., Rusch, N. J., Striessnig, J., et al. (2001). Down-regulation of L-type calcium channels in inflamed circular smooth muscle cells of the canine colon, Gastroenterology 120, 480–489.PubMedCrossRefGoogle Scholar
  29. Lu, G., Pian, X., Berezin, I., et al. (1997). Inflammation modulates in vitro colonic myoelectric and contractile activity and interstitial cells of Cajal, Am. J. Physiol. 273, G1233–G1245.PubMedGoogle Scholar
  30. Main, C., Blennerhassett, P. and Collins, S. M. (1993). Human recombinant interleukin 1 beta suppresses acetylcholine release from rat myenteric plexus, Gastroenterology 104, 1648–1654.PubMedGoogle Scholar
  31. Martinolle, J. P., Garcia-Villar, R., Fioramonti, J., et al. (1997). Altered contractility of circular and longitudinal muscle in TNBS-inflamed guinea pig ileum, Am. J. Physiol. 272, G1258–1267.PubMedGoogle Scholar
  32. Melamed-Frank, M., Terzic, A., Carrasco, A. J., et al. (2001). Reciprocal regulation of expression of pore-forming KATP channel genes by hypoxia, Mol. Cell Biochem. 225, 145–150.PubMedCrossRefGoogle Scholar
  33. Mikkelsen, H. B., Thuneberg, L., Rumessen, J. J., et al. (1985). Macrophage-like cells in the muscularis externa of mouse small intestine, Anat. Rec. 213, 77–86.PubMedCrossRefGoogle Scholar
  34. Moreels, T. G., De Man, J. G., De Winter, B. Y., et al. (2001). How to express pharmacological contractions of the inflamed rat intestine, Naunyn-Schmiedebergs Arch. Pharmacol. 364, 524–533.PubMedCrossRefGoogle Scholar
  35. Ohama, T., Hori, M., Sato, K., et al. (2003). Chronic treatment with interleukin-1β attenuates contractions by decreasing the activities of CPI-17 and MYPT-1 in intestinal smooth muscle, J. Biol. Chem. 278, 48794–48804.PubMedCrossRefGoogle Scholar
  36. Ozaki, H., Kawai, T., Shuttleworth, C. W., et al. (2004). Isolation and characterization of resident macrophages from the smooth muscle layers of murine small intestine, Neurogastroenterol. Motil. 16, 39–51.PubMedCrossRefGoogle Scholar
  37. Pfitzer, G. (2001). Invited review: regulation of myosin phosphorylation in smooth muscle, J. Appl. Physiol. 91, 497–503.PubMedGoogle Scholar
  38. Rao, S. S. and Read, N. W. (1990). Gastrointestinal motility in patients with ulcerative colitis, Scand. J. Gastroenterol. 172(Suppl.), 22–28.Google Scholar
  39. Reddy, S. N., Bazzocchi, G., Chan, S., et al. (1991). Colonic motility and transit in health and ulcerative colitis, Gastroenterology 101, 1289–1297.PubMedGoogle Scholar
  40. Rogler, G. and Andus, T. (1998). Cytokines in inflammatory bowel disease, World J. Surg. 22, 382–389.PubMedCrossRefGoogle Scholar
  41. Schwarz, N. T., Kalff, J. C., Turler, A., et al. (2004). Selective jejunal manipulation causes postoperative pan-enteric inflammation and dysmotility, Gastroenterology 126, 159–169.PubMedCrossRefGoogle Scholar
  42. Senba, S., Eto, M. and Yazawa, M. (1999). Identification of trimeric myosin phosphatase (PP1M) as a target for a novel pke-potentiated protein phosphatase-1 inhibitory protein (CPI17) in porcine aorta smooth muscle, J. Biochem. 125, 354–362.PubMedGoogle Scholar
  43. Somlyo, A. P. and Somlyo, A. V. (2000). Signal transduction by γ-proteins, Rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II, J. Physiol. 522, 177–185.PubMedCrossRefGoogle Scholar
  44. Suzuki, T., Won, K. J., Horiguchi, K., et al. (2004). Muscularis inflammation and the loss of interstitial cells of Cajal in the endothelin ETB receptor null rat, Am. J. Physiol. 287, G638–G646.Google Scholar
  45. Terzic, A., Jahangir, A. and Kurachi, Y. (1995). Cardiac ATP-sensitive K+ channels: regulation by intracellular nucleotides and K+ channel-opening drugs, Am. J. Physiol. 269, C525–C545.PubMedGoogle Scholar
  46. Vermillion, D. L., Huizinga, J. D., Riddell, R. H., et al. (1993). Altered small intestinal smooth muscle function in Crohn’s disease, Gastroenterology 104, 1692–1699.PubMedGoogle Scholar
  47. Vrees, M. D., Pricolo, V. E., Potenti, F. M., et al. (2002). Abnormal motility in patients with ulcerative colitis: the role of inflammatory cytokines, Arch. Surg. 137, 439–446.PubMedCrossRefGoogle Scholar
  48. Zhao, A., Bossone, C., Pineiro-Carrero, V., et al. (2001). Colitis-induced alterations in adrenergic control of circular smooth muscle in vitro in rats, J. Pharmacol. Exp. Ther. 299, 768–774.PubMedGoogle Scholar

Copyright information

© Brill Academic Publishers 2005

Authors and Affiliations

  • Hiroshi Ozaki
    • 1
  • Masatoshi Hori
    • 1
  • Kazuya Kinoshita
    • 1
  • Takashi Ohama
    • 1
  1. 1.Department of Veterinary Pharmacology, Graduate School of Agriculture and Life SciencesThe University of TokyoTokyoJapan

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