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Mediators of Inflammation
Volume 2012, Article ID 409580, 9 pages
http://dx.doi.org/10.1155/2012/409580
Review Article

Muscarinic Receptors and Their Antagonists in COPD: Anti-Inflammatory and Antiremodeling Effects

1Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
2Pulmonary Cell Research-Pneumology, University Hospital Basel, 4031 Basel, Switzerland

Received 13 September 2012; Accepted 12 October 2012

Academic Editor: Fábio Santos Lira

Copyright © 2012 George Karakiulakis and Michael Roth. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. Wickman, G. Krapivinsky, S. Corey et al., “Structure, G protein activation, and functional relevance of the cardiac G protein-gated K+ channel, I(KACh),” Annals of the New York Academy of Sciences, vol. 868, pp. 386–398, 1999. View at Publisher · View at Google Scholar · View at Scopus
  2. R. M. Eglen, “Muscarinic receptor subtypes in neuronal and non-neuronal cholinergic function,” Autonomic and Autacoid Pharmacology, vol. 26, no. 3, pp. 219–233, 2006. View at Publisher · View at Google Scholar · View at Scopus
  3. C. C. Felder, “Muscarinic acetylcholine receptors: signal transduction through multiple effectors,” FASEB Journal, vol. 9, no. 8, pp. 619–625, 1995. View at Google Scholar · View at Scopus
  4. R. A. Hall, R. T. Premont, and R. J. Lefkowitz, “Hetahelical receptor signaling: beyond the G protein paradigm,” Journal of Cell Biology, vol. 145, no. 5, pp. 927–932, 1999. View at Publisher · View at Google Scholar · View at Scopus
  5. M. P. Caulfield and N. J. M. Birdsall, “International union of pharmacology. XVII. Classification of muscarinic acetylcholine receptors,” Pharmacological Reviews, vol. 50, no. 2, pp. 279–290, 1998. View at Google Scholar · View at Scopus
  6. Acetylcholine Receptors (Muscarinic), IUPHAR Database of Receptors and Ion Channels, International Union of Basic and Clinical Pharmacology, http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1271.
  7. MeSH Browser, 2012, http://www.nlm.nih.gov/mesh/2012/mesh_browser/MBrowser.html.
  8. E. G. Peralta, A. Ashkenazi, J. W. Winslow, D. H. Smith, J. Ramachandran, and D. J. Capon, “Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors,” The EMBO Journal, vol. 6, no. 13, pp. 3923–3929, 1987. View at Google Scholar · View at Scopus
  9. T. I. Bonner, A. C. Young, M. R. Bran, and N. J. Buckley, “Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes,” Neuron, vol. 1, no. 5, pp. 403–410, 1988. View at Google Scholar · View at Scopus
  10. M. M. Hosey, “Diversity of structure, signaling and regulation within the family of muscarinic cholinergic receptors,” FASEB Journal, vol. 6, no. 3, pp. 845–852, 1992. View at Google Scholar · View at Scopus
  11. S. M. Forsythe, P. C. Kogut, J. F. McConville et al., “Structure and transcription of the human m3 muscarinic receptor gene,” American Journal of Respiratory Cell and Molecular Biology, vol. 26, no. 3, pp. 298–305, 2002. View at Google Scholar · View at Scopus
  12. R. M. Eglen and S. R. Nahorski, “The muscarinic M5 receptor: a silent or emerging subtype?” British Journal of Pharmacology, vol. 130, no. 1, pp. 13–21, 2000. View at Google Scholar · View at Scopus
  13. N. M. Nathanson, “A multiplicity of muscarinic mechanisms: enough signaling pathways to take your breath away,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 12, pp. 6245–6247, 2000. View at Publisher · View at Google Scholar · View at Scopus
  14. C. J. van Koppen and B. Kaiser, “Regulation of muscarinic acetylcholine receptor signaling,” Pharmacology and Therapeutics, vol. 98, no. 2, pp. 197–220, 2003. View at Publisher · View at Google Scholar · View at Scopus
  15. K. Rosenblum, M. Futter, M. Jones, E. C. Hulme, and T. V. P. Bliss, “ERKI/II regulation by the muscarinic acetylcholine receptors in neurons,” Journal of Neuroscience, vol. 20, no. 3, pp. 977–985, 2000. View at Google Scholar · View at Scopus
  16. M. Profita, A. Bonanno, A. M. Montalbano et al., “Cigarette smoke extract activates human bronchial epithelial cells affecting non-neuronal cholinergic system signalling in vitro,” Life Sciences, vol. 89, no. 1-2, pp. 36–43, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. T. A. Oenema, S. Kolahian, J. E. Nanninga et al., “Pro-inflammatory mechanisms of muscarinic receptor stimulation in airway smooth muscle,” Respiratory Research, vol. 11, article 130, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. R. Gosens, J. Zaagsma, H. Meurs, and A. J. Halayko, “Muscarinic receptor signaling in the pathophysiology of asthma and COPD,” Respiratory Research, vol. 7, article 73, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. J. C. Mak, J. N. Baraniuk, and P. J. Barnes, “Localization of muscarinic receptor subtype mRNAs in human lung,” American Journal of Respiratory Cell and Molecular Biology, vol. 7, no. 3, pp. 344–348, 1992. View at Google Scholar · View at Scopus
  20. T. Ikeda, A. S. Anisuzzaman, H. Yoshiki et al., “Regional quantification of muscarinic acetylcholine receptors and β-adrenoceptors in human airways,” British Journal of Pharmacology, vol. 166, pp. 1804–1814, 2012. View at Google Scholar
  21. L. E. Kistemaker, T. A. Oenema, H. Meurs, and R. Gosens, “Regulation of airway inflammation and remodeling by muscarinic receptors: perspectives on anticholinergic therapy in asthma and COPD,” Life Sciences, vol. 91, no. 21-22, pp. 1126–1133, 2012. View at Google Scholar
  22. J. Milara, A. Serrano, T. Peiró et al., “Aclidinium inhibits human lung fibroblast to myofibroblast transition,” Thorax, vol. 67, no. 3, pp. 229–237, 2012. View at Google Scholar
  23. J. W. J. Lammers, P. Minette, M. McCusker, and P. J. Barnes, “The role of prinzepine-sensitive (M1) muscarinic receptors in vagally mediated bronchoconstriction in humans,” American Review of Respiratory Disease, vol. 139, no. 2, pp. 446–449, 1989. View at Google Scholar · View at Scopus
  24. J. P. Gies, C. Bertrand, P. Vanderheyden et al., “Characterization of muscarinic receptors in human, guinea pig and rat lung,” Journal of Pharmacology and Experimental Therapeutics, vol. 250, no. 1, pp. 309–315, 1989. View at Google Scholar · View at Scopus
  25. H. J. Patel, P. J. Barnes, T. Takahashi, S. Tadjkarimi, M. H. Yacoub, and M. G. Belvisi, “Evidence for prejunctional muscarinic autoreceptors in human and guinea pig trachea,” American Journal of Respiratory and Critical Care Medicine, vol. 152, no. 3, pp. 872–878, 1995. View at Google Scholar · View at Scopus
  26. R. E. J. Ten Berge, J. Zaagsma, and A. F. Roffel, “Muscarinic inhibitory autoreceptors in different generations of human airways,” American Journal of Respiratory and Critical Care Medicine, vol. 154, no. 1, pp. 43–49, 1996. View at Google Scholar · View at Scopus
  27. E. Roux, M. Molimard, J. P. Savineau, and R. Marthan, “Muscarinic stimulation of airway smooth muscle cells,” General Pharmacology, vol. 31, no. 3, pp. 349–356, 1998. View at Publisher · View at Google Scholar · View at Scopus
  28. A. F. Roffel, C. R. S. Elzinga, R. G. M. Van Amsterdam, R. A. De Zeeuw, and J. Zaagsma, “Muscarinic M2 receptor in bovine tracheal smooth muscle: discrepancies between binding and function,” European Journal of Pharmacology, vol. 153, no. 1, pp. 73–82, 1988. View at Google Scholar · View at Scopus
  29. R. M. Eglen, S. S. Hegde, and N. Watson, “Muscarinic receptor subtypes and smooth muscle function,” Pharmacological Reviews, vol. 48, no. 4, pp. 531–565, 1996. View at Google Scholar · View at Scopus
  30. A. F. Roffel, C. R. Elzinga, and J. Zaagsma, “Muscarinic M3 receptors mediate contraction of human central and peripheral airway smooth muscle,” Pulmonary Pharmacology, vol. 3, no. 1, pp. 47–51, 1990. View at Publisher · View at Google Scholar · View at Scopus
  31. G. Villetti, F. Pastore, M. Bergamaschi et al., “Bronchodilator activity of (3R)-3-[[[(3-fluorophenyl) [(3,4,5-trifluorophenyl)methyl]amino]carbonyl] oxy]-1-[2-oxo-2-(2-thienyl)ethyl]-1-azoniabicyclo[2.2.2]octane bromide (CHF5407), a potent, long-acting, and selective muscarinic M3 receptor antagonist,” Journal of Pharmacology and Experimental Therapeutics, vol. 335, no. 3, pp. 622–635, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. E. J. Paredes-Gamero, V. P. Medeiros, E. H. C. Farias et al., “Heparin induces rat aorta relaxation via integrin-dependent activation of muscarinic M3 receptors,” Hypertension, vol. 56, no. 4, pp. 713–721, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. I. Wessler and C. J. Kirkpatrick, “Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans,” British Journal of Pharmacology, vol. 154, no. 8, pp. 1558–1571, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. A. Koarai, S. L. Traves, P. S. Fenwick et al., “Expression of muscarinic receptors by human macrophages,” European Respiratory Journal, vol. 39, no. 3, pp. 698–704, 2012. View at Google Scholar
  35. J. D. Moffatt, T. M. Cocks, and C. P. Page, “Role of the epithelium and acetylcholine in mediating the contraction to 5-hydroxytryptamine in the mouse isolated trachea,” British Journal of Pharmacology, vol. 141, no. 7, pp. 1159–1166, 2004. View at Publisher · View at Google Scholar · View at Scopus
  36. W. Kummer, S. Wiegand, S. Akinci et al., “Role of acetylcholine and muscarinic receptors in serotonin-induced bronchoconstriction in the mouse,” Journal of Molecular Neuroscience, vol. 30, no. 1-2, pp. 67–68, 2006. View at Publisher · View at Google Scholar · View at Scopus
  37. G. R. Petrie and K. N. V. Palmer, “Comparison of aerosol ipratropium bromide and salbutamol in chronic bronchitis and asthma,” British Medical Journal, vol. 1, no. 5955, pp. 430–432, 1975. View at Google Scholar · View at Scopus
  38. P. J. Barnes, “Tiotropium bromide,” Expert Opinion on Investigational Drugs, vol. 10, no. 4, pp. 733–740, 2001. View at Publisher · View at Google Scholar · View at Scopus
  39. B. Disse, G. A. Speck, K. L. Rominger, T. J. Witek, and R. Hammer, “Tiotropium (spiriva(TM)): mechanistical considerations and clinical profile in obstructive lung disease,” Life Sciences, vol. 64, no. 6-7, pp. 457–464, 1999. View at Publisher · View at Google Scholar · View at Scopus
  40. J. A. Ohar and J. F. Donohue, “Mono- and combination therapy of long-acting bronchodilators and inhaled corticosteroids in advanced COPD,” Seminars in Respiratory and Critical Care Medicine, vol. 31, no. 3, pp. 321–333, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. P. A. H. Minette, J. W. J. Lammers, C. M. S. Dixon, M. T. McCusker, and P. J. Barnes, “A muscarinic agonist inhibits reflex bronchoconstriction in normal but not in asthmatic subjects,” Journal of Applied Physiology, vol. 67, no. 6, pp. 2461–2465, 1989. View at Google Scholar · View at Scopus
  42. Z. Nie, D. B. Jacoby, and A. D. Fryer, “Etanercept prevents airway hyperresponsiveness by protecting neuronal M2 muscarinic receptors in antigen-challenged guinea pigs,” British Journal of Pharmacology, vol. 156, no. 1, pp. 201–210, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. D. B. Jacoby, G. J. Gleich, and A. D. Fryer, “Human eosinophil major basic protein is an endogenous allosteric antagonist at the inhibitory muscarinic M2 receptor,” Journal of Clinical Investigation, vol. 91, no. 4, pp. 1314–1318, 1993. View at Google Scholar · View at Scopus
  44. S. Matthiesen, A. Bahulayan, S. Kempkens et al., “Muscarinic receptors mediate stimulation of human lung fibroblast proliferation,” American Journal of Respiratory Cell and Molecular Biology, vol. 35, no. 6, pp. 621–627, 2006. View at Publisher · View at Google Scholar · View at Scopus
  45. P. A. Selivanova, E. S. Kulikov, O. V. Kozina, E. A. Gereng, M. B. Freidin, and L. M. Ogorodova, “Morphological and molecular characteristics of “difficult” asthma,” Journal of Asthma, vol. 47, no. 3, pp. 269–275, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. P. A. Selivanova, E. S. Kulikov, O. V. Kozina et al., “Differential expression of the β,2-adrenoreceptor and M3-cholinoreceptor genes in bronchial mucosa of patients with asthma and chronic obstructive pulmonary disease,” Annals of Allergy, Asthma & Immunology, vol. 108, no. 1, pp. 39–43, 2012. View at Google Scholar
  47. P. J. Barnes, “Immunology of asthma and chronic obstructive pulmonary disease,” Nature Reviews Immunology, vol. 8, no. 3, pp. 183–192, 2008. View at Publisher · View at Google Scholar · View at Scopus
  48. J. C. Hogg, F. Chu, S. Utokaparch et al., “The nature of small-airway obstruction in chronic obstructive pulmonary disease,” The New England Journal of Medicine, vol. 350, no. 26, pp. 2645–2653, 2004. View at Publisher · View at Google Scholar · View at Scopus
  49. A. L. James, T. R. Bai, T. Mauad et al., “Airway smooth muscle thickness in asthma is related to severity but not duration of asthma,” European Respiratory Journal, vol. 34, no. 5, pp. 1040–1045, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. P. K. Jeffery, “Remodeling in asthma and chronic obstructive lung disease,” American Journal of Respiratory and Critical Care Medicine, vol. 164, no. 10, part 2, pp. S28–38, 2001. View at Google Scholar · View at Scopus
  51. S. S. An, T. R. Bai, J. H. T. Bates et al., “Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma,” European Respiratory Journal, vol. 29, no. 5, pp. 834–860, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. R. Gosens, I. S. T. Bos, J. Zaagsma, and H. Meurs, “Protective effects of tiotropium bromide in the progression of airway smooth muscle remodeling,” American Journal of Respiratory and Critical Care Medicine, vol. 171, no. 10, pp. 1096–1102, 2005. View at Publisher · View at Google Scholar · View at Scopus
  53. C. L. Grainge, L. C. K. Lau, J. A. Ward et al., “Effect of bronchoconstriction on airway remodeling in asthma,” The New England Journal of Medicine, vol. 364, no. 21, pp. 2006–2015, 2011. View at Publisher · View at Google Scholar · View at Scopus
  54. S. Goulet, M. P. Bihl, F. Gambazzi, M. Tamm, and M. Roth, “Opposite effect of corticosteroids and long-acting β2- agonits on serum- and TGF-β1-induced extracellular matrix deposition by primary human lung fibroblasts,” Journal of Cellular Physiology, vol. 210, no. 1, pp. 167–176, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. E. A. Kelly and N. N. Jarjour, “Role of matrix metalloproteinases in asthma,” Current Opinion in Pulmonary Medicine, vol. 9, no. 1, pp. 28–33, 2003. View at Publisher · View at Google Scholar · View at Scopus
  56. D. F. Rogers, “Motor control of airway goblet cells and glands,” Respiration Physiology, vol. 125, no. 1-2, pp. 129–144, 2001. View at Publisher · View at Google Scholar · View at Scopus
  57. E. J. Morcillo and J. Cortijo, “Mucus and MUC in asthma,” Current Opinion in Pulmonary Medicine, vol. 12, no. 1, pp. 1–6, 2006. View at Publisher · View at Google Scholar · View at Scopus
  58. J. Cortijo, M. Mata, J. Milara et al., “Aclidinium inhibits cholinergic and tobacco smoke-induced MUC5AC in human airways,” European Respiratory Journal, vol. 37, no. 2, pp. 244–254, 2011. View at Publisher · View at Google Scholar · View at Scopus
  59. T. Pera, A. Zuidhof, J. Valadas et al., “Tiotropium inhibits pulmonary inflammation and remodelling in a guinea pig model of COPD,” European Respiratory Journal, vol. 38, no. 4, pp. 789–796, 2011. View at Google Scholar
  60. I. S. T. Bos, R. Gosens, A. B. Zuidhof et al., “Inhibition of allergen-induced airway remodelling by tiotropium and budesonide: a comparison,” European Respiratory Journal, vol. 30, no. 4, pp. 653–661, 2007. View at Publisher · View at Google Scholar · View at Scopus
  61. N. Arai, M. Kondo, T. Izumo, J. Tamaoki, and A. Nagai, “Inhibition of neutrophil elastase-induced goblet cell metaplasia by tiotropium in mice,” European Respiratory Journal, vol. 35, no. 5, pp. 1164–1171, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. J. Metzen, F. Bittinger, C. J. Kirkpatrick, H. Kilbinger, and I. Wessler, “Proliferative effect of acetylcholine on rat trachea epithelial cells is mediated by nicotinic receptors and muscarinic receptors of the M1-subtype,” Life Sciences, vol. 72, no. 18-19, pp. 2075–2080, 2003. View at Publisher · View at Google Scholar · View at Scopus
  63. B. J. Proskocil, H. S. Sekhon, Y. Jia et al., “Acetylcholine is an autocrine or paracrine hormone synthesized and secreted by airway bronchial epithelial cells,” Endocrinology, vol. 145, no. 5, pp. 2498–2506, 2004. View at Publisher · View at Google Scholar · View at Scopus
  64. S. Haag, S. Matthiesen, U. R. Juergens, and K. Racké, “Muscarinic receptors mediate stimulation of collagen synthesis in human lung fibroblasts,” European Respiratory Journal, vol. 32, no. 3, pp. 555–562, 2008. View at Publisher · View at Google Scholar · View at Scopus
  65. M. Profita, A. Bonanno, L. Siena et al., “Smoke, choline acetyltransferase, muscarinic receptors, and fibroblast proliferation in chronic obstructive pulmonary disease,” Journal of Pharmacology and Experimental Therapeutics, vol. 329, no. 2, pp. 753–763, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. K. C. Kong, C. K. Billington, U. Gandhi, R. A. Panettieri, and R. B. Penn, “Cooperative mitogenic signaling by G protein-coupled receptors and growth factors is dependent on G(q/11),” The FASEB Journal, vol. 20, no. 9, pp. 1558–1560, 2006. View at Publisher · View at Google Scholar · View at Scopus
  67. R. Gosens, G. Dueck, E. Rector et al., “Cooperative regulation of GSK-3 by muscarinic and PDGF receptors is associated with airway myocyte proliferation,” American Journal of Physiology, vol. 293, no. 5, pp. L1348–L1358, 2007. View at Publisher · View at Google Scholar · View at Scopus
  68. N. J. Fairbank, S. C. Connolly, J. D. MacKinnon, K. Wehry, L. Deng, and G. N. Maksym, “Airway smooth muscle cell tone amplifies contractile function in the presence of chronic cyclic strain,” American Journal of Physiology, vol. 295, no. 3, pp. L479–L488, 2008. View at Publisher · View at Google Scholar · View at Scopus
  69. T. A. Oenema, M. Smit, L. Smedinga et al., “Muscarinic receptor stimulation augments TGF-β,1-induced contractile protein expression by airway smooth muscle cells,” American Journal of Physiology, vol. 303, no. 7, pp. L589–L597, 2012. View at Google Scholar
  70. S. Ohta, N. Oda, T. Yokoe et al., “Effect of tiotropium bromide on airway inflammation and remodelling in a mouse model of asthma,” Clinical and Experimental Allergy, vol. 40, no. 8, pp. 1266–1275, 2010. View at Publisher · View at Google Scholar · View at Scopus
  71. R. Cao, X. W. Dong, J. X. Jiang et al., “M3 muscarinic receptor antagonist bencycloquidium bromide attenuates allergic airway inflammation, hyperresponsiveness and remodeling in mice,” European Journal of Pharmacology, vol. 655, no. 1–3, pp. 83–90, 2011. View at Publisher · View at Google Scholar · View at Scopus
  72. E. Papakonstantinou, A. J. Aletras, M. Roth, M. Tamm, and G. Karakiulakis, “Hypoxia modulates the effects of transforming growth factor-β isoforms on matrix-formation by primary human lung fibroblasts,” Cytokine, vol. 24, no. 1-2, pp. 25–35, 2003. View at Publisher · View at Google Scholar · View at Scopus
  73. G. Karakiulakis, E. Papakonstantinou, A. J. Aletras, M. Tamm, and M. Roth, “Cell type-specific effect of hypoxia and platelet-derived growth factor-BB on extracellular matrix turnover and its consequences for lung remodeling,” Journal of Biological Chemistry, vol. 282, no. 2, pp. 908–915, 2007. View at Publisher · View at Google Scholar · View at Scopus
  74. V. Lagente and E. Boichot, “Role of matrix metalloproteinases in the inflammatory process of respiratory diseases,” Journal of Molecular and Cellular Cardiology, vol. 48, no. 3, pp. 440–444, 2010. View at Publisher · View at Google Scholar · View at Scopus
  75. E. Papakonstantinou and G. Karakiulakis, “The “sweet” and “bitter” involvement of glycosaminoglycans in lung diseases: pharmacotherapeutic relevance,” British Journal of Pharmacology, vol. 157, no. 7, pp. 1111–1127, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. I. Klagas, S. Goulet, G. Karakiulakis et al., “Decreased hyaluronan in airway smooth muscle cells from patients with asthma and COPD,” European Respiratory Journal, vol. 34, no. 3, pp. 616–628, 2009. View at Publisher · View at Google Scholar · View at Scopus
  77. D. Cataldo, C. Munaut, A. Noël et al., “MMP-2- and MMP-9-linked gelatinolytic activity in the sputum from patients with asthma and chronic obstructive pulmonary disease,” International Archives of Allergy and Immunology, vol. 123, no. 3, pp. 259–267, 2000. View at Google Scholar · View at Scopus
  78. K. Imai, S. S. Dalal, E. S. Chen et al., “Human collagenase (matrix metalloproteinase-1) expression in the lungs of patients with emphysema,” American Journal of Respiratory and Critical Care Medicine, vol. 163, no. 3 I, pp. 786–791, 2001. View at Google Scholar · View at Scopus
  79. K. Asano, Y. Shikama, Y. Shibuya et al., “Suppressive activity of tiotropium bromide on matrix metalloproteinase production from lung fibroblasts in vitro,” International Journal of COPD, vol. 3, no. 4, pp. 781–790, 2008. View at Google Scholar · View at Scopus
  80. K. Asano, Y. Shikama, N. Shoji, K. Hirano, H. Suzaki, and H. Nakajima, “Tiotropium bromide inhibits TGF-β-induced MMP production from lung fibroblasts by interfering with Smad and MAPK pathways in vitro,” International Journal of Chronic Obstructive Pulmonary Disease, vol. 5, pp. 277–286, 2010. View at Google Scholar · View at Scopus
  81. G. Xie, K. Cheng, J. Shant, and J. P. Raufman, “Acetylcholine-induced activation of M3 muscarinic receptors stimulates robust matrix metalloproteinase gene expression in human colon cancer cells,” American Journal of Physiology, vol. 296, no. 4, pp. G755–G763, 2009. View at Publisher · View at Google Scholar · View at Scopus
  82. E. Papakonstantinou, M. Roth, and G. Karakiulakis, “Isolation and characterization of glycosaminoglycans from human atheromatous vessels,” Methods in Molecular Medicine, vol. 52, pp. 123–136, 2001. View at Google Scholar
  83. C. H. Yeh, H. S. Chiang, and C. T. Chien, “Hyaluronic acid ameliorates bladder hyperactivity via the inhibition of H2O2-enhanced purinergic and muscarinic signaling in the rat,” Neurourology and Urodynamics, vol. 29, no. 5, pp. 765–770, 2010. View at Publisher · View at Google Scholar · View at Scopus
  84. T. Krieg, L. Cui, Q. Qin, M. V. Cohen, and J. M. Downey, “Mitochondrial ROS generation following acetylcholine-induced EGF receptor transactivation requires metalloproteinase cleavage of proHB-EGF,” Journal of Molecular and Cellular Cardiology, vol. 36, no. 3, pp. 435–443, 2004. View at Publisher · View at Google Scholar · View at Scopus
  85. D. Mears and C. L. Zimliki, “Muscarinic agonists activate Ca2+ store-operated and -independent ionic currents in insulin-secreting HIT-T15 cells and mouse pancreatic β-cells,” Journal of Membrane Biology, vol. 197, no. 1, pp. 59–70, 2004. View at Publisher · View at Google Scholar · View at Scopus
  86. I. Stelmach, J. Jerzyńska, M. Bobrowska, A. Brzozowska, P. Majak, and P. Kuna, “The effect of inhaled heparin on airway responsiveness to metacholine in asthmatic children,” Polskie Archiwum Medycyny Wewnetrznej, vol. 106, no. 1, pp. 567–572, 2001. View at Google Scholar · View at Scopus
  87. T. Ahmed, J. Garrigo, and I. Danta, “Preventing bronchoconstriction in exercise-induced asthma with inhaled heparin,” The New England Journal of Medicine, vol. 329, no. 2, pp. 90–95, 1993. View at Publisher · View at Google Scholar · View at Scopus