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Muscarinic Receptor Antagonists: Effects on Pulmonary Function

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Book cover Muscarinic Receptors

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 208))

Abstract

In healthy lungs, muscarinic receptors control smooth muscle tone, mucus secretion, vasodilation, and inflammation. In chronic obstructive pulmonary disease (COPD) and asthma, cholinergic mechanisms contribute to increased bronchoconstriction and mucus secretion that limit airflow. This chapter reviews neuronal and nonneuronal sources of acetylcholine in the lung and the expression and role of M1, M2, and M3 muscarinic receptor subtypes in lung physiology. It also discusses the evidence for and against the role of parasympathetic nerves in asthma, and the current use and therapeutic potential of muscarinic receptor antagonists in COPD and asthma.

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Abbreviations

ChAT:

Choline acetyltransferase

COPD:

Chronic obstructive pulmonary disease

FEV1 :

Forced expiratory volume in 1 s

References

  • Adamko DJ, Yost BL, Gleich GJ, Fryer AD, Jacoby DB (1999) Ovalbumin sensitization changes the inflammatory response to subsequent parainfluenza infection. Eosinophils mediate airway hyperresponsiveness, m(2) muscarinic receptor dysfunction, and antiviral effects. J Exp Med 190:1465–1478

    PubMed  CAS  Google Scholar 

  • Anthonisen NR, Connett JE, Kiley JP, Altose MD, Bailey WC, Buist AS, Conway WA Jr, Enright PL, Kanner RE, O’Hara P et al (1994) Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study. JAMA 272:1497–1505

    PubMed  CAS  Google Scholar 

  • Aquilina AT, Hall WJ, Douglas RG Jr, Utell MJ (1980) Airway reactivity in subjects with viral upper respiratory tract infections: the effects of exercise and cold air. Am Rev Respir Dis 122:3–10

    PubMed  CAS  Google Scholar 

  • Ayala LE, Ahmed T (1989) Is there loss of protective muscarinic receptor mechanism in asthma? Chest 96:1285–1291

    PubMed  CAS  Google Scholar 

  • Bai TR (1990) Abnormalities in airway smooth muscle in fatal asthma. Am Rev Respir Dis 141:552–557

    PubMed  CAS  Google Scholar 

  • Baigelman W, Chodosh S (1977) Bronchodilator action of the anticholinergic drug, ipratropium bromide (Sch 1000), as an aerosol in chronic bronchitis and asthma. Chest 71:324–328

    PubMed  CAS  Google Scholar 

  • Baker B, Peatfield AC, Richardson PS (1985) Nervous control of mucin secretion into human bronchi. J Physiol 365:297–305

    PubMed  CAS  Google Scholar 

  • Baker DG, McDonald DM, Basbaum CB, Mitchell RA (1986) The architecture of nerves and ganglia of the ferret trachea as revealed by acetylcholinesterase histochemistry. J Comp Neurol 246:513–526

    PubMed  CAS  Google Scholar 

  • Baker DG, Don HF, Brown JK (1992) Direct measurement of acetylcholine release in guinea pig trachea. Am J Physiol 263:L142–L147

    PubMed  CAS  Google Scholar 

  • Balogh G, Dimitrov-Szokodi D, Husveti A (1957) Lung denervation in the therapy of intractable bronchial asthma. J Thorac Surg 33:166–184

    PubMed  CAS  Google Scholar 

  • Baroody F, Wagenmann M, Naclerio R (1993) Comparison of the secretory response of the nasal mucosa to methacholine and histamine. J Appl Physiol 74:2661–2671

    PubMed  CAS  Google Scholar 

  • Basbaum C (1984) Innervation of the airway mucosa and submucosa. Semin Respir Med 5:308–313

    Google Scholar 

  • Belmonte KE, Fryer AD, Costello RW (1998) Role of insulin in antigen-induced airway eosinophilia and neuronal M2 muscarinic receptor dysfunction. J Appl Physiol 85:1708–1718

    PubMed  CAS  Google Scholar 

  • Blaber LC, Fryer AD, Maclagan J (1985) Neuronal muscarinic receptors attenuate vagally-induced contraction of feline bronchial smooth muscle. Br J Pharmacol 86:723–728

    PubMed  CAS  Google Scholar 

  • Bloom JW, Baumgartener-Folkerts C, Palmer JD, Yamamura HI, Halonen M (1988) A muscarinic receptor subtype modulates vagally stimulated bronchial contraction. J Appl Physiol 65:2144–2150

    PubMed  CAS  Google Scholar 

  • Borson DB, Charlin M, Gold BD, Nadel JA (1984) Neural regulation of 35SO4-macromolecule secretion from tracheal glands of ferrets. J Appl Physiol 57:457–466

    PubMed  CAS  Google Scholar 

  • Borut TC, Tashkin DP, Fischer TJ, Katz R, Rachelefsky G, Siegel SC, Lee E, Harper C (1977) Comparison of aerosolized atropine sulfate and SCH 1000 on exercise-induced bronchospasm in children. J Allergy Clin Immunol 60:127–133

    PubMed  CAS  Google Scholar 

  • Bos IS, Gosens R, Zuidhof AB, Schaafsma D, Halayko AJ, Meurs H, Zaagsma J (2007) Inhibition of allergen-induced airway remodelling by tiotropium and budesonide: a comparison. Eur Respir J 30:653–661

    PubMed  CAS  Google Scholar 

  • Boushey H, Richardson P, Widdicombe J (1972) Reflex effects of laryngeal irritation on the pattern of breathing and total lung resistance. J Physiol 224:501–513

    PubMed  CAS  Google Scholar 

  • Buhling F, Lieder N, Kuhlmann UC, Waldburg N, Welte T (2007) Tiotropium suppresses acetylcholine-induced release of chemotactic mediators in vitro. Respir Med 101:2386–2394

    PubMed  Google Scholar 

  • Cabezas GA, Graf PD, Nadel JA (1971) Sympathetic versus parasympathetic nervous regulation of airways in dogs. J Appl Physiol 31:651–655

    PubMed  CAS  Google Scholar 

  • Canning BJ, Fischer A (1997) Localization of cholinergic nerves in lower airways of guinea pigs using antisera to choline acetyltransferase. Am J Physiol 272:L731–L738

    PubMed  CAS  Google Scholar 

  • Casaburi R, Briggs DD Jr, Donohue JF, Serby CW, Menjoge SS, Witek TJ Jr (2000) The spirometric efficacy of once-daily dosing with tiotropium in stable COPD: a 13-week multicenter trial. The US Tiotropium Study Group. Chest 118:1294–1302

    PubMed  CAS  Google Scholar 

  • Casarosa P, Bouyssou T, Germeyer S, Schnapp A, Gantner F, Pieper M (2009) Preclinical evaluation of long-acting muscarinic antagonists: comparison of tiotropium and investigational drugs. J Pharmacol Exp Ther 330:660–668

    PubMed  CAS  Google Scholar 

  • Casterline CL, Evans R III, Ward GW Jr (1976) The effect of atropine and albuterol aerosols on the human bronchial response to histamine. J Allergy Clin Immunol 58:607–613

    PubMed  CAS  Google Scholar 

  • Catterall JR, Rhind GB, Whyte KF, Shapiro CM, Douglas NJ (1988) Is nocturnal asthma caused by changes in airway cholinergic activity? Thorax 43:720–724

    PubMed  CAS  Google Scholar 

  • Caulfield MP, Birdsall NJ (1998) International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacol Rev 50:279–290

    PubMed  CAS  Google Scholar 

  • Cavallotti C, D’Andrea V, Cavallotti C, Cameroni M (2005) Distribution of acetylcholinesterase and cholineacetyl-transferase activities in the human pulmonary vessels of younger and older adults. Geriatr Gerontol Int 5:286–292

    Google Scholar 

  • Chan-Yeung M (1977) The effect of Sch 1000 and disodium cromoglycate on exercise-induced asthma. Chest 71:320–323

    PubMed  CAS  Google Scholar 

  • Chan-Yeung MM, Vyas MN, Grzybowski S (1971) Exercise-induced asthma. Am Rev Respir Dis 104:915–923

    PubMed  CAS  Google Scholar 

  • Chen WY, Brenner AM, Weiser PC, Chai H (1981) Atropine and exercise-induced bronchoconstriction. Chest 79:651–656

    PubMed  CAS  Google Scholar 

  • Cockcroft DW, Ruffin RE, Hargreave FE (1978) Effect of Sch1000 in allergen-induced asthma. Clin Allergy 8:361–372

    PubMed  CAS  Google Scholar 

  • Colebatch HJ, Halmagyi DF (1963) Effect of vagotomy and vagal stimulation on lung mechanics and circulation. J Appl Physiol 18:881–887

    PubMed  CAS  Google Scholar 

  • Corssen G, Allen CR (1959) Acetylcholine: its significance in controlling ciliary activity of human respiratory epithelium in vitro. J Appl Physiol 14:901–904

    PubMed  CAS  Google Scholar 

  • Costello RW, Schofield BH, Kephart GM, Gleich GJ, Jacoby DB, Fryer AD (1997) Localization of eosinophils to airway nerves and effect on neuronal M2 muscarinic receptor function. Am J Physiol 273:L93–L103

    PubMed  CAS  Google Scholar 

  • Dale HH (1914) The action of certain esters and ethers of choline, and their relation to muscarine. J Pharmacol Exp Ther 6:147–190

    CAS  Google Scholar 

  • Daniel EE, Kannan M, Davis C, Posey-Daniel V (1986) Ultrastructural studies on the neuromuscular control of human tracheal and bronchial muscle. Respir Physiol 63:109–128

    PubMed  CAS  Google Scholar 

  • Disse B, Reichl R, Speck G, Traunecker W, Ludwig Rominger KL, Hammer R (1993) Ba 679 BR, a novel long-acting anticholinergic bronchodilator. Life Sci 52:537–544

    PubMed  CAS  Google Scholar 

  • Dowling MR, Charlton SJ (2006) Quantifying the association and dissociation rates of unlabelled antagonists at the muscarinic M3 receptor. Br J Pharmacol 148:927–937

    PubMed  CAS  Google Scholar 

  • Dusser D, Bravo ML, Iacono P (2006) The effect of tiotropium on exacerbations and airflow in patients with COPD. Eur Respir J 27:547–555

    PubMed  CAS  Google Scholar 

  • Dwyer TM, Szebeni A, Diveki K, Farley JM (1992) Transient cholinergic glycoconjugate secretion from swine tracheal submucosal gland cells. Am J Physiol 262:L418–L426

    PubMed  CAS  Google Scholar 

  • Elbon CL, Jacoby DB, Fryer AD (1995) Pretreatment with an antibody to interleukin-5 prevents loss of pulmonary M2 muscarinic receptor function in antigen-challenged guinea pigs. Am J Respir Cell Mol Biol 12:320–328

    PubMed  CAS  Google Scholar 

  • Empey DW, Laitinen LA, Jacobs L, Gold WM, Nadel JA (1976) Mechanisms of bronchial hyperreactivity in normal subjects after upper respiratory tract infection. Am Rev Respir Dis 113:131–139

    PubMed  CAS  Google Scholar 

  • Ensing K, de Zeeuw RA, Nossent GD, Koeter GH, Cornelissen PJ (1989) Pharmacokinetics of ipratropium bromide after single dose inhalation and oral and intravenous administration. Eur J Clin Pharmacol 36:189–194

    PubMed  CAS  Google Scholar 

  • Evans CM, Fryer AD, Jacoby DB, Gleich GJ, Costello RW (1997) Pretreatment with antibody to eosinophil major basic protein prevents hyperresponsiveness by protecting neuronal M2 muscarinic receptors in antigen-challenged guinea pigs. J Clin Invest 100:2254–2262

    PubMed  CAS  Google Scholar 

  • Ferguson SM, Savchenko V, Apparsundaram S, Zwick M, Wright J, Heilman CJ, Yi H, Levey AI, Blakely RD (2003) Vesicular localization and activity-dependent trafficking of presynaptic choline transporters. J Neurosci 23:9697–9709

    PubMed  CAS  Google Scholar 

  • Fernandes LB, Fryer AD, Hirshman CA (1992) M2 muscarinic receptors inhibit isoproterenol-induced relaxation of canine airway smooth muscle. J Pharmacol Exp Ther 262:119–126

    PubMed  CAS  Google Scholar 

  • Fish JE, Rosenthal RR, Summer WR, Menkes H, Norman PS, Permutt S (1977) The effect of atropine on acute antigen-mediated airway constriction in subjects with allergic asthma. Am Rev Respir Dis 115:371–379

    PubMed  CAS  Google Scholar 

  • Fisher HK, Holton P, Buxton RS, Nadel JA (1970) Resistance to breathing during exercise-induced asthma attacks. Am Rev Respir Dis 101:885–896

    PubMed  CAS  Google Scholar 

  • Fisher JT, Vincent SG, Gomeza J, Yamada M, Wess J (2004) Loss of vagally mediated bradycardia and bronchoconstriction in mice lacking M2 or M3 muscarinic acetylcholine receptors. FASEB J 18:711–713

    PubMed  CAS  Google Scholar 

  • Fryer AD, Jacoby DB (1991) Parainfluenza virus infection damages inhibitory M2 muscarinic receptors on pulmonary parasympathetic nerves in the guinea-pig. Br J Pharmacol 102:267–271

    PubMed  CAS  Google Scholar 

  • Fryer AD, Jacoby DB (1992) Function of pulmonary M2 muscarinic receptors in antigen-challenged guinea pigs is restored by heparin and poly-l-glutamate. J Clin Invest 90:2292–2298

    PubMed  CAS  Google Scholar 

  • Fryer AD, Maclagan J (1984) Muscarinic inhibitory receptors in pulmonary parasympathetic nerves in the guinea-pig. Br J Pharmacol 83:973–978

    PubMed  CAS  Google Scholar 

  • Fryer AD, Wills-Karp M (1991) Dysfunction of M2-muscarinic receptors in pulmonary parasympathetic nerves after antigen challenge. J Appl Physiol 71:2255–2261

    PubMed  CAS  Google Scholar 

  • Fryer AD, el-Fakahany EE, Jacoby DB (1990) Parainfluenza virus type 1 reduces the affinity of agonists for muscarinic receptors in guinea-pig lung and heart. Eur J Pharmacol 181:51–58

    PubMed  CAS  Google Scholar 

  • Fryer AD, Elbon CL, Kim AL, Xiao HQ, Levey AI, Jacoby DB (1996) Cultures of airway parasympathetic nerves express functional M2 muscarinic receptors. Am J Respir Cell Mol Biol 15:716–725

    PubMed  CAS  Google Scholar 

  • Fryer AD, Stein LH, Nie Z, Curtis DE, Evans CM, Hodgson ST, Jose PJ, Belmonte KE, Fitch E, Jacoby DB (2006) Neuronal eotaxin and the effects of CCR3 antagonist on airway hyperreactivity and M2 receptor dysfunction. J Clin Invest 116:228–236

    PubMed  CAS  Google Scholar 

  • Fujimura M, Kamio Y, Matsuda T (1992) Effect of a M1-selective muscarinic receptor antagonist (pirenzepine) on basal bronchomotor tone in young women. Respiration 59:102–106

    PubMed  CAS  Google Scholar 

  • Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376

    PubMed  CAS  Google Scholar 

  • Gallagher JT, Kent PW, Passatore M, Phipps RJ, Richardson PS (1975) The composition of tracheal mucus and the nervous control of its secretion in the cat. Proc R Soc Lond B Biol Sci 192:49–76

    PubMed  CAS  Google Scholar 

  • Godfrey S, Konig P (1975) Suppression of exercise-induced asthma by salbutamol, theophylline, atropine, cromolyn, and placebo in a group of asthmatic children. Pediatrics 56:930–934

    PubMed  CAS  Google Scholar 

  • GOLD (2009) Global initiative for chronic obstructive lung disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. National Heart Lung and Blood Institute, World Health Organization. http://www.goldcopd.com. Accessed 8 July 2010

  • Gold WM, Kessler GF, Yu DY (1972) Role of vagus nerves in experimental asthma in allergic dogs. J Appl Physiol 33:719–725

    PubMed  CAS  Google Scholar 

  • Goodman LS, Gilman A, Brunton LL, Lazo JS, Parker KL (2006) Goodman & Gilman’s the pharmacological basis of therapeutics, 11th edn. McGraw-Hill, New York, NY

    Google Scholar 

  • Gosens R, Nelemans SA, Grootte Bromhaar MM, McKay S, Zaagsma J, Meurs H (2003) Muscarinic M3-receptors mediate cholinergic synergism of mitogenesis in airway smooth muscle. Am J Respir Cell Mol Biol 28:257–262

    PubMed  CAS  Google Scholar 

  • Gosens R, Bos IS, Zaagsma J, Meurs H (2005) Protective effects of tiotropium bromide in the progression of airway smooth muscle remodeling. Am J Respir Crit Care Med 171:1096–1102

    PubMed  Google Scholar 

  • Greenberg B, Rhoden K, Barnes PJ (1987) Endothelium-dependent relaxation of human pulmonary arteries. Am J Physiol 252:H434–H438

    PubMed  CAS  Google Scholar 

  • Gross NJ, Skorodin MS (1984) Anticholinergic, antimuscarinic bronchodilators. Am Rev Respir Dis 129:856–870

    PubMed  CAS  Google Scholar 

  • Gross NJ, Co E, Skorodin MS (1989) Cholinergic bronchomotor tone in COPD. Estimates of its amount in comparison with that in normal subjects. Chest 96:984–987

    PubMed  CAS  Google Scholar 

  • Haag S, Matthiesen S, Juergens UR, Racke K (2008) Muscarinic receptors mediate stimulation of collagen synthesis in human lung fibroblasts. Eur Respir J 32:555–562

    PubMed  CAS  Google Scholar 

  • Haberberger R, Schemann M, Sann H, Kummer W (1997) Innervation pattern of guinea pig pulmonary vasculature depends on vascular diameter. J Appl Physiol 82:426–434

    PubMed  CAS  Google Scholar 

  • Haberberger RV, Bodenbenner M, Kummer W (2000) Expression of the cholinergic gene locus in pulmonary arterial endothelial cells. Histochem Cell Biol 113:379–387

    PubMed  CAS  Google Scholar 

  • Haddad EB, Landry Y, Gies JP (1991) Muscarinic receptor subtypes in guinea pig airways. Am J Physiol 261:L327–L333

    PubMed  CAS  Google Scholar 

  • Haddad EB, Mak JC, Belvisi MG, Nishikawa M, Rousell J, Barnes PJ (1996) Muscarinic and beta-adrenergic receptor expression in peripheral lung from normal and asthmatic patients. Am J Physiol 270:L947–L953

    PubMed  CAS  Google Scholar 

  • Holtzman M, Sheller J, Dimeo M, Nadel J, Boushey H (1980) Effect of ganglionic blockade on bronchial reactivity in atopic subjects. Am Rev Respir Dis 122:17–25

    PubMed  CAS  Google Scholar 

  • Holtzman MJ, McNamara MP, Sheppard D, Fabbri LM, Hahn HL, Graf PD, Nadel JA (1983) Intravenous versus inhaled atropine for inhibiting bronchoconstrictor responses in dogs. J Appl Physiol 54:134–139

    PubMed  CAS  Google Scholar 

  • Iwamoto H, Yokoyama A, Shiota N, Shoda H, Haruta Y, Hattori N, Kohno N (2008) Tiotropium bromide is effective for severe asthma with noneosinophilic phenotype. Eur Respir J 31:1379–1380

    PubMed  CAS  Google Scholar 

  • Jacoby DB, Gleich GJ, Fryer AD (1993) Human eosinophil major basic protein is an endogenous allosteric antagonist at the inhibitory muscarinic M2 receptor. J Clin Invest 91:1314–1318

    PubMed  CAS  Google Scholar 

  • Jacoby DB, Xiao HQ, Lee NH, Chan-Li Y, Fryer AD (1998) Virus- and interferon-induced loss of inhibitory M2 muscarinic receptor function and gene expression in cultured airway parasympathetic neurons. J Clin Invest 102:242–248

    PubMed  CAS  Google Scholar 

  • Jammes Y, Mei N (1979) Assessment of the pulmonary origin of bronchoconstrictor vagal tone. J Physiol 291:305–316

    PubMed  CAS  Google Scholar 

  • Jositsch G, Papadakis T, Haberberger RV, Wolff M, Wess J, Kummer W (2009) Suitability of muscarinic acetylcholine receptor antibodies for immunohistochemistry evaluated on tissue sections of receptor gene-deficient mice. Naunyn Schmiedebergs Arch Pharmacol 379:389–395

    PubMed  CAS  Google Scholar 

  • Kalia M (1981) Brain stem localization of vagal preganglionic neurons. J Auton Nerv Syst 3:451–481

    PubMed  CAS  Google Scholar 

  • Kesler BS, Canning BJ (1999) Regulation of baseline cholinergic tone in guinea-pig airway smooth muscle. J Physiol 518(Pt 3):843–855

    PubMed  CAS  Google Scholar 

  • Klein MK, Haberberger RV, Hartmann P, Faulhammer P, Lips KS, Krain B, Wess J, Kummer W, Konig P (2009) Muscarinic receptor subtypes in cilia-driven transport and airway epithelial development. Eur Respir J 33:1113–1121

    PubMed  CAS  Google Scholar 

  • Knight DS, Ellison JP, Hibbs RG, Hyman AL, Kadowitz PJ (1981) A light and electron microscopic study of the innervation of pulmonary arteries in the cat. Anat Rec 201:513–521

    PubMed  CAS  Google Scholar 

  • Koyama S, Rennard SI, Robbins RA (1992) Acetylcholine stimulates bronchial epithelial cells to release neutrophil and monocyte chemotactic activity. Am J Physiol 262:L466–L471

    PubMed  CAS  Google Scholar 

  • Koyama S, Sato E, Nomura H, Kubo K, Nagai S, Izumi T (1998) Acetylcholine and substance P stimulate bronchial epithelial cells to release eosinophil chemotactic activity. J Appl Physiol 84:1528–1534

    PubMed  CAS  Google Scholar 

  • Krymskaya VP, Orsini MJ, Eszterhas AJ, Brodbeck KC, Benovic JL, Panettieri RA Jr, Penn RB (2000) Mechanisms of proliferation synergy by receptor tyrosine kinase and G protein-coupled receptor activation in human airway smooth muscle. Am J Respir Cell Mol Biol 23:546–554

    PubMed  CAS  Google Scholar 

  • Kummer W, Haberberger R (1999) Extrinsic and intrinsic cholinergic systems of the vascular wall. Eur J Morphol 37:223–226

    PubMed  CAS  Google Scholar 

  • Kummer W, Wiegand S, Akinci S, Wessler I, Schinkel AH, Wess J, Koepsell H, Haberberger RV, Lips KS (2006) Role of acetylcholine and polyspecific cation transporters in serotonin-induced bronchoconstriction in the mouse. Respir Res 7:65

    PubMed  Google Scholar 

  • Laitinen LA, Laitinen MV, Widdicombe JG (1987) Parasympathetic nervous control of tracheal vascular resistance in the dog. J Physiol 385:135–146

    PubMed  CAS  Google Scholar 

  • Levine RM (1959) The intestinal absorption of the quaternary derivatives of atropine and scopolamine. Arch Int Pharmacodyn Ther 121:146–149

    PubMed  CAS  Google Scholar 

  • Lips KS, Volk C, Schmitt BM, Pfeil U, Arndt P, Miska D, Ermert L, Kummer W, Koepsell H (2005) Polyspecific cation transporters mediate luminal release of acetylcholine from bronchial epithelium. Am J Respir Cell Mol Biol 33:79–88

    PubMed  CAS  Google Scholar 

  • Littner MR, Ilowite JS, Tashkin DP, Friedman M, Serby CW, Menjoge SS, Witek TJ Jr (2000) Long-acting bronchodilation with once-daily dosing of tiotropium (Spiriva) in stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med 161:1136–1142

    PubMed  CAS  Google Scholar 

  • Liu QH, Zheng YM, Korde AS, Yadav VR, Rathore R, Wess J, Wang YX (2009) Membrane depolarization causes a direct activation of G protein-coupled receptors leading to local Ca2+ release in smooth muscle. Proc Natl Acad Sci USA 106:11418–11423

    PubMed  CAS  Google Scholar 

  • Maesen FP, Smeets JJ, Sledsens TJ, Wald FD, Cornelissen PJ (1995) Tiotropium bromide, a new long-acting antimuscarinic bronchodilator: a pharmacodynamic study in patients with chronic obstructive pulmonary disease (COPD). Dutch Study Group. Eur Respir J 8:1506–1513

    PubMed  CAS  Google Scholar 

  • Mak J, Barnes P (1990) Autoradiographic visualization of muscarinic receptor subtypes in human and guinea pig lung. Am Rev Respir Dis 141:1559–1568

    PubMed  CAS  Google Scholar 

  • Mak JC, Baraniuk JN, Barnes PJ (1992) Localization of muscarinic receptor subtype mRNAs in human lung. Am J Respir Cell Mol Biol 7:344–348

    PubMed  CAS  Google Scholar 

  • Matthiesen S, Bahulayan A, Kempkens S, Haag S, Fuhrmann M, Stichnote C, Juergens UR, Racke K (2006) Muscarinic receptors mediate stimulation of human lung fibroblast proliferation. Am J Respir Cell Mol Biol 35:621–627

    PubMed  CAS  Google Scholar 

  • Matthiesen S, Bahulayan A, Holz O, Racke K (2007) MAPK pathway mediates muscarinic receptor-induced human lung fibroblast proliferation. Life Sci 80:2259–2262

    PubMed  CAS  Google Scholar 

  • McAllen R, Spyer K (1978) Two types of vagal preganglionic motoneurones projecting to the heart and lungs. J Physiol 282:353–364

    PubMed  CAS  Google Scholar 

  • McFadden ER Jr, Luparello T, Lyons HA, Bleecker E (1969) The mechanism of action of suggestion in the induction of acute asthma attacks. Psychosom Med 31:134–143

    PubMed  Google Scholar 

  • McMahon TJ, Kadowitz PJ (1992) Methylene blue inhibits neurogenic cholinergic vasodilator responses in the pulmonary vascular bed of the cat. Am J Physiol 263:L575–L584

    PubMed  CAS  Google Scholar 

  • Minette PA, Lammers JW, Dixon CM, McCusker MT, Barnes PJ (1989) A muscarinic agonist inhibits reflex bronchoconstriction in normal but not in asthmatic subjects. J Appl Physiol 67:2461–2465

    PubMed  CAS  Google Scholar 

  • Morrison JF, Pearson SB, Dean HG (1988) Parasympathetic nervous system in nocturnal asthma. Br Med J (Clin Res Ed) 296:1427–1429

    CAS  Google Scholar 

  • Murai Y, Ishibashi H, Akaike N, Ito Y (1998) Acetylcholine modulation of high-voltage-activated calcium channels in the neurones acutely dissociated from rat paratracheal ganglia. Br J Pharmacol 123:1441–1449

    PubMed  CAS  Google Scholar 

  • Myers AC (2001) Transmission in autonomic ganglia. Respir Physiol 125:99–111

    PubMed  CAS  Google Scholar 

  • Myers AC, Undem BJ (1996) Muscarinic receptor regulation of synaptic transmission in airway parasympathetic ganglia. Am J Physiol 270:L630–L636

    PubMed  CAS  Google Scholar 

  • Nadel JA, Salem H, Tamplin B, Tokiwa Y (1965) Mechanism of Bronchoconstriction during Inhalation of Sulfur Dioxide. J Appl Physiol 20:164–167

    PubMed  CAS  Google Scholar 

  • Nakamura T, Nakanishi T, Haruta T, Shirasaka Y, Keogh JP, Tamai I (2010) Transport of ipratropium, an anti-chronic obstructive pulmonary disease drug, is mediated by organic cation/carnitine transporters in human bronchial epithelial cells: implications for carrier-mediated pulmonary absorption. Mol Pharm 7:187–195

    PubMed  CAS  Google Scholar 

  • NHLBI (2007) National Heart, Lung, and Blood Institute. Expert panel report 3 (EPR3): guidelines for the diagnosis and management of asthma. U.S. Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute. http://purl.access.gpo.gov/GPO/LPS93946. Accessed 8 July 2010

  • Nie Z, Jacoby DB, Fryer AD (2009) Etanercept prevents airway hyperresponsiveness by protecting neuronal M2 muscarinic receptors in antigen-challenged guinea pigs. Br J Pharmacol 156:201–210

    PubMed  CAS  Google Scholar 

  • Niewoehner DE, Rice K, Cote C, Paulson D, Cooper JA Jr, Korducki L, Cassino C, Kesten S (2005) Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial. Ann Intern Med 143:317–326

    PubMed  CAS  Google Scholar 

  • Olsen C, Colebatch H, Mebel P, Nadel J, Staub N (1965) Motor control of pulmonary airways studied by nerve stimulation. J Appl Physiol 20:202–208

    Google Scholar 

  • Overholt RH (1959) Pulmonary denervation and resection in asthmatic patients. Ann Allergy 17:534–545

    Google Scholar 

  • Phillips EW, Scott WJM (1929) The surgical treatment of bronchial asthma. Arch Surg 19:1425–1456

    Google Scholar 

  • Pieper MP, Chaudhary NI, Park JE (2007) Acetylcholine-induced proliferation of fibroblasts and myofibroblasts in vitro is inhibited by tiotropium bromide. Life Sci 80:2270–2273

    PubMed  CAS  Google Scholar 

  • Pradidarcheep W, Labruyere WT, Dabhoiwala NF, Lamers WH (2008) Lack of specificity of commercially available antisera: better specifications needed. J Histochem Cytochem 56:1099–1111

    PubMed  CAS  Google Scholar 

  • Proskocil BJ, Sekhon HS, Jia Y, Savchenko V, Blakely RD, Lindstrom J, Spindel ER (2004) Acetylcholine is an autocrine or paracrine hormone synthesized and secreted by airway bronchial epithelial cells. Endocrinology 145:2498–2506

    PubMed  CAS  Google Scholar 

  • Ramnarine SI, Haddad EB, Khawaja AM, Mak JC, Rogers DF (1996) On muscarinic control of neurogenic mucus secretion in ferret trachea. J Physiol 494(Pt 2):577–586

    PubMed  CAS  Google Scholar 

  • Rebuck AS, Marcus HI (1979) SCH 1000 in psychogenic asthma. Scand J Respir Dis Suppl 103:186–191

    PubMed  CAS  Google Scholar 

  • Reinheimer T, Bernedo P, Klapproth H, Oelert H, Zeiske B, Racke K, Wessler I (1996) Acetylcholine in isolated airways of rat, guinea pig, and human: species differences in role of airway mucosa. Am J Physiol 270:L722–L728

    PubMed  CAS  Google Scholar 

  • Reinheimer T, Baumgartner D, Hohle KD, Racke K, Wessler I (1997) Acetylcholine via muscarinic receptors inhibits histamine release from human isolated bronchi. Am J Respir Crit Care Med 156:389–395

    PubMed  CAS  Google Scholar 

  • Reinheimer T, Munch M, Bittinger F, Racke K, Kirkpatrick CJ, Wessler I (1998) Glucocorticoids mediate reduction of epithelial acetylcholine content in the airways of rats and humans. Eur J Pharmacol 349:277–284

    PubMed  CAS  Google Scholar 

  • Reinheimer T, Mohlig T, Zimmermann S, Hohle KD, Wessler I (2000) Muscarinic control of histamine release from airways. Inhibitory M1-receptors in human bronchi but absence in rat trachea. Am J Respir Crit Care Med 162:534–538

    PubMed  CAS  Google Scholar 

  • Roberts JA, Raeburn D, Rodger IW, Thomson NC (1984) Comparison of in vivo airway responsiveness and in vitro smooth muscle sensitivity to methacholine in man. Thorax 39:837–843

    PubMed  CAS  Google Scholar 

  • Roberts AM, Coleridge HM, Coleridge JC (1988) Reciprocal action of pulmonary vagal afferents on tracheal smooth muscle tension in dogs. Respir Physiol 72:35–46

    PubMed  CAS  Google Scholar 

  • Rodrigo GJ, Castro-Rodriguez JA (2005) Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis. Thorax 60:740–746

    PubMed  CAS  Google Scholar 

  • Rodrigo GJ, Rodrigo C (2000) First-line therapy for adult patients with acute asthma receiving a multiple-dose protocol of ipratropium bromide plus albuterol in the emergency department. Am J Respir Crit Care Med 161:1862–1868

    PubMed  CAS  Google Scholar 

  • Roffel AF, in’t Hout WG, de Zeeuw RA, Zaagsma J (1987) The M2 selective antagonist AF-DX 116 shows high affinity for muscarine receptors in bovine tracheal membranes. Naunyn Schmiedebergs Arch Pharmacol 335:593–595

    PubMed  CAS  Google Scholar 

  • Roffel AF, Elzinga CR, Van Amsterdam RG, De Zeeuw RA, Zaagsma J (1988) Muscarinic M2 receptors in bovine tracheal smooth muscle: discrepancies between binding and function. Eur J Pharmacol 153:73–82

    PubMed  CAS  Google Scholar 

  • Roffel AF, Elzinga CR, Zaagsma J (1990) Muscarinic M3 receptors mediate contraction of human central and peripheral airway smooth muscle. Pulm Pharmacol 3:47–51

    PubMed  CAS  Google Scholar 

  • Rogers DF (2001) Motor control of airway goblet cells and glands. Respir Physiol 125:129–144

    PubMed  CAS  Google Scholar 

  • Rosenthal RR, Norman PS, Summer WR, Permutt S (1977) Role of the parasympathetic system in antigen-induced bronchospasm. J Appl Physiol 42:600–606

    PubMed  CAS  Google Scholar 

  • Ruffin RE, Cockcroft DW, Hargreave FE (1978) A comparison of the protective effect of fenoterol and Sch 1000 on allergen-induced asthma. J Allergy Clin Immunol 61:42–47

    PubMed  CAS  Google Scholar 

  • Salathe M, Lipson EJ, Ivonnet PI, Bookman RJ (1997) Muscarinic signaling in ciliated tracheal epithelial cells: dual effects on Ca2+ and ciliary beating. Am J Physiol 272:L301–L310

    PubMed  CAS  Google Scholar 

  • Schultheis AH, Bassett DJ, Fryer AD (1994) Ozone-induced airway hyperresponsiveness and loss of neuronal M2 muscarinic receptor function. J Appl Physiol 76:1088–1097

    PubMed  CAS  Google Scholar 

  • Severinghaus JW, Stupfel M (1955) Respiratory dead space increase following atropine in man, and atropine, vagal or ganglionic blockade and hypothermia in dogs. J Appl Physiol 8:81–87

    PubMed  CAS  Google Scholar 

  • Seybold ZV, Mariassy AT, Stroh D, Kim CS, Gazeroglu H, Wanner A (1990) Mucociliary interaction in vitro: effects of physiological and inflammatory stimuli. J Appl Physiol 68:1421–1426

    PubMed  CAS  Google Scholar 

  • Sheppard D, Epstein J, Holtzman M, Nadel J, Boushey H (1982) Dose-dependent inhibition of cold air-induced bronchoconstriction by atropine. J Appl Physiol: Respir Environ Exercise Physiol 53:169–174

    PubMed  CAS  Google Scholar 

  • Sheppard D, Epstein J, Holtzman MJ, Nadel JA, Boushey HA (1983) Effect of route of atropine delivery on bronchospasm from cold air and methacholine. J Appl Physiol 54:130–133

    PubMed  CAS  Google Scholar 

  • Stengel PW, Gomeza J, Wess J, Cohen ML (2000) M(2) and M(4) receptor knockout mice: muscarinic receptor function in cardiac and smooth muscle in vitro. J Pharmacol Exp Ther 292:877–885

    PubMed  CAS  Google Scholar 

  • Struckmann N, Schwering S, Wiegand S, Gschnell A, Yamada M, Kummer W, Wess J, Haberberger RV (2003) Role of muscarinic receptor subtypes in the constriction of peripheral airways: studies on receptor-deficient mice. Mol Pharmacol 64:1444–1451

    PubMed  CAS  Google Scholar 

  • Takahashi T, Belvisi MG, Patel H, Ward JK, Tadjkarimi S, Yacoub MH, Barnes PJ (1994) Effect of Ba 679 BR, a novel long-acting anticholinergic agent, on cholinergic neurotransmission in guinea pig and human airways. Am J Respir Crit Care Med 150:1640–1645

    PubMed  CAS  Google Scholar 

  • Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M (2008) A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 359:1543–1554

    PubMed  CAS  Google Scholar 

  • Undem BJ, Myers AC, Barthlow H, Weinreich D (1990) Vagal innervation of guinea pig bronchial smooth muscle. J Appl Physiol 69:1336–1346

    PubMed  CAS  Google Scholar 

  • van Koppen CJ, Blankesteijn WM, Klaassen AB, Rodrigues de Miranda JF, Beld AJ, van Ginneken CA (1987) Autoradiographic visualization of muscarinic receptors in pulmonary nerves and ganglia. Neurosci Lett 83:237–240

    PubMed  Google Scholar 

  • van Koppen CJ, Blankesteijn WM, Klaassen AB, Rodrigues de Miranda JF, Beld AJ, van Ginneken CA (1988) Autoradiographic visualization of muscarinic receptors in human bronchi. J Pharmacol Exp Ther 244:760–764

    PubMed  Google Scholar 

  • van Noord JA, Smeets JJ, Custers FL, Korducki L, Cornelissen PJ (2002) Pharmacodynamic steady state of tiotropium in patients with chronic obstructive pulmonary disease. Eur Respir J 19:639–644

    PubMed  Google Scholar 

  • Virtanen R, Kanto J, Iisalo E, Iisalo EU, Salo M, Sjovall S (1982) Pharmacokinetic studies on atropine with special reference to age. Acta Anaesthesiol Scand 26:297–300

    PubMed  CAS  Google Scholar 

  • Wagner EM, Jacoby DB (1999) Methacholine causes reflex bronchoconstriction. J Appl Physiol 86:294–297

    PubMed  CAS  Google Scholar 

  • Wessler I, Holper B, Kortsik C, Buhl R, Kilbinger H, Kirkpatrick CJ (2007) Dysfunctional inhibitory muscarinic receptors mediate enhanced histamine release in isolated human bronchi. Life Sci 80:2294–2297

    PubMed  CAS  Google Scholar 

  • Whicker SD, Armour CL, Black JL (1988) Responsiveness of bronchial smooth muscle from asthmatic patients to relaxant and contractile agonists. Pulm Pharmacol 1:25–31

    PubMed  CAS  Google Scholar 

  • Widdicombe JG (1966) Action potentials in parasympathetic and sympathetic efferent fibres to the trachea and lungs of dogs and cats. J Physiol 186:56–88

    PubMed  CAS  Google Scholar 

  • Widdicombe JG, Kent DC, Nadel JA (1962) Mechanism of bronchoconstriction during inhalation of dust. J Appl Physiol 17:613–616

    PubMed  CAS  Google Scholar 

  • Woenne R, Kattan M, Orange RP, Levison H (1978) Bronchial hyperreactivity to histamine and methacholine in asthmatic children after inhalation of SCH 1000 and chlorpheniramine maleate. J Allergy Clin Immunol 62:119–124

    PubMed  CAS  Google Scholar 

  • Wong LB, Miller IF, Yeates DB (1988) Stimulation of ciliary beat frequency by autonomic agonists: in vivo. J Appl Physiol 65:971–981

    PubMed  CAS  Google Scholar 

  • Yang CM, Farley JM, Dwyer TM (1988) Muscarinic stimulation of submucosal glands in swine trachea. J Appl Physiol 64:200–209

    PubMed  CAS  Google Scholar 

  • Yost BL, Gleich GJ, Fryer AD (1999) Ozone-induced hyperresponsiveness and blockade of M2 muscarinic receptors by eosinophil major basic protein. J Appl Physiol 87:1272–1278

    PubMed  CAS  Google Scholar 

  • Yu DY, Galant SP, Gold WM (1972) Inhibition of antigen-induced bronchoconstriction by atropine in asthmatic patients. J Appl Physiol 32:823–828

    PubMed  CAS  Google Scholar 

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  1. Oregon Health and Science University, 3181 SW Sam Jackson Park Road, UHN67, Portland, OR, 97239, USA

    Kalmia S. Buels & Allison D. Fryer

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  1. Kalmia S. Buels
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  2. Allison D. Fryer
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  1. UHN67, Department of Pulmonary and Critical Ca, Oregon Health & Science University, SW Sam Jackson Park Road 3181, Portland, 97239, Oregon, USA

    Allison D. Fryer

  2. , Department of Pharmacology, Monash Institute of Pharmaceutical Scien, Royal Parade 381, Parkville, 3052, Victoria, Australia

    Arthur Christopoulos

  3. , Department of Pharmacology, University of Washington, Seattle, 98195-7750, Washington, USA

    Neil M. Nathanson

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Buels, K.S., Fryer, A.D. (2012). Muscarinic Receptor Antagonists: Effects on Pulmonary Function. In: Fryer, A., Christopoulos, A., Nathanson, N. (eds) Muscarinic Receptors. Handbook of Experimental Pharmacology, vol 208. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-23274-9_14

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