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Persistent and selective effects of inflammation on smooth muscle cell contractility in rat colitis

  • Gastrointestinal Function
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Abstract

Intestinal inflammation affects smooth muscle contractility contributing to altered motility, but changes to the individual smooth muscle cells are not well described. We used video microscopy to study the contractility of circular smooth muscle cells (CSMC) isolated from the rat mid-descending colon throughout the course of TNBS-induced colitis, measuring their shortening response to carbachol (CCh), 5-HT, histamine or high K+. In control CSMC, CCh caused a maximal shortening response of 28 (2%), similar to that for 5-HT of 27 (1%), but by day 4 of colitis, these responses were decreased by 35% and 37%, respectively. By day 36, all aspects of cholinergic contraction returned to control levels, while 5-HT-induced contraction remained significantly attenuated. In contrast, the contractile responses to histamine remained similar at all time points. K+-induced contraction was impaired only on day 4, and the maximal response remained substantially greater than CCh or 5-HT. Colitis caused a 121% increase in CSMC length by day 2 that persisted through day 36, independent evidence for phenotypic change. We conclude that impaired CSMC contractility at both the receptor and non-receptor levels contribute to altered smooth muscle function during colitis. Persistent changes in contractile response remained detectable after resolution of inflammation, and similar events may occur in post-enteritis syndromes seen in humans.

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References

  1. Akbarali HI, Pothoulakis C, 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  CAS  Google Scholar 

  2. Akiho H, Blennerhassett P, Deng Y, Collins SM (2002) Role of IL-4, IL-13, and STAT6 in inflammation-induced hypercontractility of murine smooth muscle cells. Am J Physiol 282:G226–G232

    CAS  Google Scholar 

  3. Bhounsule SA, D’Sa S, Fernandes N, D’Souza RD, Dhume VG (1996) Gastrointestinal actions of buprenorphine: are different receptors involved? Eur J Pharmacol 316:253–256

    Article  CAS  PubMed  Google Scholar 

  4. Blennerhassett MG, Lourenssen S (2000) Neural regulation of intestinal smooth muscle growth in vitro. Am J Physiol 279:G511–G519

    CAS  Google Scholar 

  5. Blennerhassett MG, Vignjevic P, Vermillion DL, Collins SM (1992) Inflammation causes hyperplasia and hypertrophy in smooth muscle of rat small intestine. Am J Physiol 262:G1041–G1046

    CAS  PubMed  Google Scholar 

  6. Blennerhassett MG, Bovell FM, Lourenssen S, McHugh KM (1999) Characteristics of inflammation-induced hypertrophy of rat intestinal smooth muscle cell. Dig Dis Sci 44:1265–1272

    Article  CAS  PubMed  Google Scholar 

  7. Castro GA, Badial-Aceves F, Smith JW, Dudrick SJ, Weisbrodt NW (1976) Altered small bowel propulsion associated with parasitism. Gastroenterology 71:620–625

    CAS  PubMed  Google Scholar 

  8. Collins SM (1996) The immunomodulation of enteric neuromuscular function: implications for motility and inflammatory disorders. Gastroenterology 111:1683–1699

    CAS  PubMed  Google Scholar 

  9. Collins SM, Gardner JD (1982) Cholecystokinin-induced contraction of dispersed smooth muscle cells. Am J Physiol 243:G497–G504

    CAS  PubMed  Google Scholar 

  10. Depoortere I, Van Assche G, Thijs T, Geboes K, Peeters TL (1999) Differential changes in ACh-, motilin-, substance P-, and K(+)-induced contractility in rabbit colitis. Am J Physiol 277:G61–G68

    CAS  PubMed  Google Scholar 

  11. Elson CO, Sartor RB, Tennyson GS, Riddell RH (1995) Experimental models of inflammatory bowel disease. Gastroenterology 109:1344–1367

    CAS  PubMed  Google Scholar 

  12. Farthing MJ (1998) New drugs in the management of the irritable bowel syndrome. Drugs 56:11–21

    CAS  Google Scholar 

  13. Gabella G (1975) Hypertrophy of intestinal smooth muscle. Cell Tissue Res 163:199–214

    CAS  PubMed  Google Scholar 

  14. Grider JR (2003) Neurotransmitters mediating the intestinal peristaltic reflex in the mouse. J Pharmacol Exp Ther 307:460–467

    Article  CAS  PubMed  Google Scholar 

  15. Halayko AJ, Salari H, MA X, Stephens NL (1996) Markers of airway smooth muscle cell phenotype. Am J Physiol 270:L1040–L1051

    CAS  PubMed  Google Scholar 

  16. Hogaboam CM, Jacobson K, Collins SM, Blennerhassett MG (1995) The selective beneficial effects of nitric oxide inhibition in experimental colitis. Am J Physiol 268:G673–G684

    CAS  PubMed  Google Scholar 

  17. Krawisz JE, Sharon P, Stenson WF (1984) Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterology 87:1344–1350

    CAS  PubMed  Google Scholar 

  18. Kuemmerle JF, Martin DC, Murthy KS, Kellum JM, Grider JR, Makhlouf GM (1992) Coexistence of contractile and relaxant 5-hydroxytryptamine receptors coupled to distinct signaling pathways in intestinal muscle cells: convergence of the pathways on Ca2+ mobilization. Mol Pharmacol 42:1090–1096

    CAS  PubMed  Google Scholar 

  19. Linden DR, Chen JX, Gershon MD, Sharkey KA, Mawe GM (2003) Serotonin availability is increased in mucosa of guinea pigs with TNBS-induced colitis. Am J Physiol 285:G207–G216

    CAS  Google Scholar 

  20. Liu X, Rusch NJ, Striessnig J, Sarna SK (2001) Down-regulation of L-type calcium channels in inflamed circular smooth muscle cells of the canine colon. Gastroenterology 120:480–489

    CAS  PubMed  Google Scholar 

  21. Lourenssen S, Jeromin A, Roder J, Blennerhassett MG (2002) Intestinal inflammation modulates expression of the synaptic vesicle protein neuronal calcium sensor-1. Am J Physiol 282:G1097–G1104

    CAS  Google Scholar 

  22. Lu G, Mazet B, Sun C, Qian X, Johnson CP, Adams MB, Roman RJ, Sarna SK (1999) Inflammatory modulation of calcium-activated potassium channels in canine colonic circular smooth muscle cells. Gastroenterology 116:884–892

    CAS  PubMed  Google Scholar 

  23. Martinolle JP, Garcia-Villar R, Fioramonti J, Bueno L (1997) Altered contractility of circular and longitudinal muscle in TNBS- inflamed guinea pig ileum. Am J Physiol 272:G1258–G1267

    CAS  PubMed  Google Scholar 

  24. Mitchell RW, Halayko AJ, Kahraman S, Solway J, Wylam ME (2000) Selective restoration of calcium coupling to muscarinic M(3) receptors in contractile cultured airway myocytes. Am J Physiol 278:L1091–L1100

    CAS  Google Scholar 

  25. Moreels TG, De Man JG, Dick JM, Nieuwendijk RJ, De Winter BY, Lefebvre RA, Herman AG, Pelckmans PA (2001) Effect of TNBS-induced morphological changes on pharmacological contractility of the rat ileum. Eur J Pharmacol 423:211–222

    Article  CAS  PubMed  Google Scholar 

  26. Morini G, Kuemmerle JF, Impicciatore M, Grider JR, Makhlouf GM (1993) Coexistence of histamine H1 and H2 receptors coupled to distinct signal transduction pathways in isolated intestinal muscle cells. J Pharmacol Exp Ther 264:598–603

    CAS  PubMed  Google Scholar 

  27. Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL (1989) Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96:795–803

    CAS  PubMed  Google Scholar 

  28. Myers BS, Martin JS, Dempsey DT, Parkman HP, Thomas RM, Ryan JP (1997) Acute experimental colitis decreases colonic circular smooth muscle contractility in rats. Am J Physiol 273:G928–G936

    CAS  PubMed  Google Scholar 

  29. Parronchi P, Romagnani P, Annunziato F, Sampognaro S, Becchio A, Giannarini L, Maggi E, Pupilli C, Tonelli F, Romagnani S (1997) Type 1 T-helper cell predominance and interleukin-12 expression in the gut of patients with Crohn’s disease. Am J Pathol 150:823–832

    CAS  PubMed  Google Scholar 

  30. Rich H, Sohn UD, Behar J, Kim N, Biancani P (1997) Experimental esophagitis affects intracellular calcium stores in the cat lower esophageal sphincter. Am J Physiol 272:G1523–G1529

    CAS  PubMed  Google Scholar 

  31. Sanovic S, Lamb DP, Blennerhassett MG (1999) Damage to the enteric nervous system in experimental colitis. Am J Pathol 155:1051–1057

    CAS  PubMed  Google Scholar 

  32. Sawa Y, Oshitani N, Adachi K, Higuchi K, Matsumoto T, Arakawa T (2003) Comprehensive analysis of intestinal cytokine messenger RNA profile by real-time quantitative polymerase chain reaction in patients with inflammatory bowel disease. Int J Mol Med 11:175–179

    CAS  Google Scholar 

  33. Shi XZ, Sarna SK (1999) Differential inflammatory modulation of canine ileal longitudinal and circular muscle cells. Am J Physiol 277:G341–G350

    CAS  PubMed  Google Scholar 

  34. Shi XZ, Sarna SK (2000) Impairment of Ca(2+) mobilization in circular muscle cells of the inflamed colon. Am J Physiol 278:G234–G242

    CAS  Google Scholar 

  35. Sohn UD, Harnett KM, Cao W, Rich H, Kim N, Behar J, Biancani P (1997) Acute experimental esophagitis activates a second signal transduction pathway in cat smooth muscle from the lower esophageal sphincter. J Pharmacol Exp Ther 283:1293–1304

    CAS  PubMed  Google Scholar 

  36. Takahara H, Fujimura M, Taniguchi S, Hayashi N, Nakamura T, Fujimiya M (2001) Changes in serotonin levels and 5-HT receptor activity in duodenum of streptozotocin-diabetic rats. Am J Physiol 281:G798–G808

    CAS  Google Scholar 

  37. Wallace JL, Keenan CM (1990) An orally active inhibitor of leukotriene synthesis accelerates healing in a rat model of colitis. Am J Physiol 258:G527–G534

    CAS  PubMed  Google Scholar 

  38. Weisbrodt NW, Lai M, Bowers RL, Harari Y, Castro GA (1994) Structural and molecular changes in intestinal smooth muscle induced by Trichinella spiralis infection. Am J Physiol 266:G856–G862

    CAS  PubMed  Google Scholar 

  39. Wells RW, Morris GP, Blennerhassett MG, Paterson WG (2003) Effects of acid-induced esophagitis on esophageal smooth muscle. Can J Physiol Pharmacol 81:451–458

    Article  CAS  PubMed  Google Scholar 

  40. Xie YN, Gerthoffer WT, Reddy SN, Cominelli F, Eysselein VE, Snape WJ Jr (1992) An abnormal rate of actin myosin cross-bridge cycling in colonic smooth muscle associated with experimental colitis. Am J Physiol 262:G921–G926

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the Canadian Institutes of Health Research (CIHR). We thank the Canadian Digestive Health Foundation and CIHR for scholarship support (R.W.W.). The authors thank Dr. S. Lourenssen for help in preparation of this manuscript.

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  1. Gastrointestinal Diseases Research Unit, Queen’s University, Kingston, Ontario, K7L 5G2, Canada

    R. W. Wells & M. G. Blennerhassett

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  1. R. W. Wells
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  2. M. G. Blennerhassett
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Correspondence to M. G. Blennerhassett.

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Wells, R.W., Blennerhassett, M.G. Persistent and selective effects of inflammation on smooth muscle cell contractility in rat colitis. Pflugers Arch - Eur J Physiol 448, 515–524 (2004). https://doi.org/10.1007/s00424-004-1286-1

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  • DOI: https://doi.org/10.1007/s00424-004-1286-1

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