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

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Abstract

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.

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References

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Collins, S. M. (1996). The immunomodulation of enteric neuromuscular function: implications for motility and inflammatory disorders, Gastroenterology 111, 1683–1699.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Fiocchi, C. (1998). Inflammatory bowel disease: etiology and pathogenesis, Gastroenterology 115, 182–205.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Hori, M. and Karaki, H. (1998). Regulatory mechanisms of calcium sensitization of contractile elements in smooth muscle, Life Sci. 62, 1629–1633.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • Hurst, S. and Collins, S. M. (1993). Interleukin-1 beta modulation of norepinephrine release from rat myenteric nerves, Am. J. Physiol. 264, G30–G35.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • Kamm, K. E. and Stull, J. T. (1989). Regulation of smooth muscle contractile elements by second messengers, Annu. Rev. Physiol. 51, 299–313.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Pfitzer, G. (2001). Invited review: regulation of myosin phosphorylation in smooth muscle, J. Appl. Physiol. 91, 497–503.

    PubMed  CAS  Google Scholar 

  • Rao, S. S. and Read, N. W. (1990). Gastrointestinal motility in patients with ulcerative colitis, Scand. J. Gastroenterol. 172(Suppl.), 22–28.

    CAS  Google Scholar 

  • Reddy, S. N., Bazzocchi, G., Chan, S., et al. (1991). Colonic motility and transit in health and ulcerative colitis, Gastroenterology 101, 1289–1297.

    PubMed  CAS  Google Scholar 

  • Rogler, G. and Andus, T. (1998). Cytokines in inflammatory bowel disease, World J. Surg. 22, 382–389.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

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Correspondence to Hiroshi Ozaki.

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Ozaki, H., Hori, M., Kinoshita, K. et al. Intestinal dysmotility in inflammatory bowel disease: Mechanisms of the reduced activity of smooth muscle contraction. Inflammopharmacol 13, 103–111 (2005). https://doi.org/10.1163/156856005774423773

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