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New Bronchodilator Drugs

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Pharmacology and Therapeutics of Asthma and COPD

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 161))

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Abstract

β 2-Adrenoceptor agonists are the gold standard for the symptomatic treatment of asthma, resulting in quick and effective bronchodilator relief, although they are not completely free from side-effects. A range of different pharmacological approaches is being actively pursued in order to achieve relaxation of airway smooth muscle comparable to that seen with β 2-adrenoceptor agonists and by mechanisms distinct from activation of theβ-adrenoceptor without attendant side-effects. These various approaches include signalling via vasoactive intestinal polypeptide (VIP) receptors, activation of soluble and particulate guanylyl cyclase, inhibition of phosphodiesterase (PDE)3 and opening of potassium channels. The pharmacology, clinical experience and merit of each of these novel approaches are discussed.

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References

  • Abderrahmane A, Salvail D, Dumoulin M, Garon J, Cadieux A, Rousseau E (1998) Direct activation of K(Ca) channel in airway smooth muscle by nitric oxide: involvement of a nitrothiosylation mechanism? Am J Respir Cell Mol Biol 19: 485–497

    PubMed  CAS  Google Scholar 

  • Adamou JE, Aiyar N, Van Horn S, Elshourbagy NA (1995) Cloning and functional characterization of the human vasoactive intestinal peptide (VIP)-2 receptor. Biochem Biophys Res Commun 209: 385–392

    Article  PubMed  CAS  Google Scholar 

  • Adda S, Fleischmann BK, Freedman BD, Yu M, Hay DW, Kotlikoff MI (1996) Expression and function of voltage-dependent potassium channel genes in human airway smooth muscle. J Biol Chem 271: 13239–13243

    Article  PubMed  CAS  Google Scholar 

  • Altiere RJ, Diamond L (1984) VIP as a bronchodilator. Lancet 1: 162–163

    Article  PubMed  CAS  Google Scholar 

  • Angus RM, McCallum MJ, Thomson NC (1994a) Effect of inhaled atrial natriuretic peptide on methacholine induced bronchoconstriction in asthma Clin Exp Allergy 24: 784–788

    CAS  Google Scholar 

  • Angus RM, Millar EA, Chalmers GW, Thomson NC (1995) Effect of inhaled atrial natriuretic peptide and a neutral endopeptidase inhibitor on histamine-induced bronchoconstriction. Am J Respir Crit Care Med 151: 2003–2005

    PubMed  CAS  Google Scholar 

  • Angus RM, Nally JE, McCall R, Young LC, McGrath JC, Thomson NC (1994b) Modulation of the effect of atrial natriuretic peptide in human and bovine bronchi by phosphoramidon. Clin Sci (Lond) 86: 291–295

    CAS  Google Scholar 

  • Bardin PG, Dorward MA, Lampe FC, Franke B, Holgate ST (1998) Effect of selective phosphodiesterase 3 inhibition on the early and late asthmatic responses to inhaled allergen. Br J Clin Pharmacol 45: 387–391

    Article  PubMed  CAS  Google Scholar 

  • Bernareggi M, Mitchell JA, Barnes PJ, Belvisi MG (1997) Dual action of nitric oxide on airway plasma leakage. Am J Respir Crit Care Med 155: 869–874

    PubMed  CAS  Google Scholar 

  • Billington CK, Joseph SK, Swan C, Scott MG, Jobson TM, Hall IP (1999) Modulation of human airway smooth muscle proliferation by type 3 phosphodiesterase inhibition. Am J Physiol 276: L412 - L419

    PubMed  CAS  Google Scholar 

  • Black JL, Armour CL, Johnson PR, Alouan LA, Barnes PJ (1990) The action of a potassium channel activator, BRL 38227 (lemakalim), on human airway smooth muscle. Am Rev Respir Dis 142: 1384–1389

    PubMed  CAS  Google Scholar 

  • Blease K, Kunkel SL, Hogaboam CM (2000) Acute inhibition of nitric oxide exacerbates airway hyperresponsiveness, eosinophilia and C-C chemokine generation in a murine model of fungal asthma. Inflamm Res 49: 297–304

    Article  PubMed  CAS  Google Scholar 

  • Bolin DR, Cottrell J, Garippa R, Michalewsky J, Rinaldi N, Simko B, O’Donnell M (1995) Structure-activity studies on the vasoactive intestinal peptide pharmacophore. 1. Analogs of tyrosine. Int J Pept Protein Res 46: 279–289

    Google Scholar 

  • Buchheit KH, Hofmann A (1996) KATP channel openers reverse immune complex-induced airways hyperreactivity independently of smooth muscle relaxation. Naunyn Schmiedebergs Arch Pharmacol 354: 355–361

    Article  PubMed  CAS  Google Scholar 

  • Buchheit KH, Manley PW, Quast U, Russ U, Mazzoni L, Fozard JR (2002) KCO912: a potent and selective opener of ATP-dependent potassium ( K(ATP)) channels which suppresses airways hyperreactivity at doses devoid of cardiovascular effects. Naunyn Schmiedebergs Arch Pharmacol 365: 220–230

    Google Scholar 

  • Bundgaard A, Enehjelm SD, Aggestrup S (1983) Pretreatment of exercise-induced asthma with inhaled vasoactive intestinal peptide (VIP). Eur J Respir Dis Suppl 128 (Pt 2): 427–429

    PubMed  Google Scholar 

  • Busto R, Carrero I, Guijarro LG, Solano RM, Zapatero J, Noguerales F, Prieto JC (1999) Expression, pharmacological, and functional evidence for PACAP/VIP receptors in human lung. Am J Physiol 277: L42 - L48

    PubMed  CAS  Google Scholar 

  • Busto R, Prieto JC, Bodega G, Zapatero J, Carrero I (2000) Immunohistochemical localization and distribution of VIP/PACAP receptors in human lung. Peptides 21: 265–269

    Article  PubMed  CAS  Google Scholar 

  • Candenas ML, Naline E, Puybasset L, Devillier P, Advenier C (1991) Effect of atrial natriuretic peptide and on atriopeptins on the human isolated bronchus. Comparison with the reactivity of the guinea-pig isolated trachea. Pulm Pharmacol 4: 120–125

    Google Scholar 

  • Carstairs JR, Barnes PJ (1986) Visualization of vasoactive intestinal peptide receptors in human and guinea pig lung. J Pharmacol Exp Ther 239: 249–255

    PubMed  CAS  Google Scholar 

  • Chapman ID, Mazzoni L, Morley J (1991) Actions of SDZ PCO 400 and cromakalim on airway smooth muscle in vivo. Agents Actions Suppl 34: 53–62

    Article  PubMed  CAS  Google Scholar 

  • Corompt E, Bessard G, Lantuejoul S, Naline E, Advenier C, Devillier P (1998) Inhibitory effects of large Ca2+-activated K+ channel blockers on beta-adrenergic-and NO-donor-mediated relaxations of human and guinea-pig airway smooth muscles. Naunyn Schmiedebergs Arch Pharmacol 357: 77–86

    Article  PubMed  CAS  Google Scholar 

  • Cortijo J, Sarria B, Pedros C, Perpina M, Paris F, Morcillo E (1992) The relaxant effects of cromakalim (BRL 34915) on human isolated airway smooth muscle. Naunyn Schmiedebergs Arch Pharmacol 346: 462–468

    PubMed  CAS  Google Scholar 

  • Cui Y, Tran S, Tinker A, Clapp LH (2002) The molecular composition of K(ATP) channels in human pulmonary artery smooth muscle cells and their modulation by growth. Am J Respir Cell Mol Biol 26: 135–143

    PubMed  CAS  Google Scholar 

  • de Boer J, Philpott AJ, van Amsterdam RG, Shahid M, Zaagsma J, Nicholson CD (1992) Human bronchial cyclic nucleotide phosphodiesterase isoenzymes: biochemical and pharmacological analysis using selective inhibitors. Br J Pharmacol 106: 1028–1034

    Article  PubMed  Google Scholar 

  • De Sanctis GT, MacLean JA, Hamada K, Mehta S, Scott JA, Jiao A, Yandava CN, Kobzik L, Wolyniec WW, Fabian AJ, Venugopal CS, Grasemann H, Huang PL, Drazen JM (1999) Contribution of nitric oxide synthases 1, 2, and 3 to airway hyperresponsiveness and inflammation in a murine model of asthma. J Exp Med 189: 1621–1630

    Article  PubMed  Google Scholar 

  • De Sanctis GT, Mehta S, Kobzik L, Yandava C, Jiao A, Huang PL, Drazen JM (1997) Contribution of type I NOS to expired gas NO and bronchial responsiveness in mice. Am J Physiol 273: L883 - L888

    PubMed  Google Scholar 

  • Dweik RA, Comhair SA, Gaston B, Thunnissen FB, Farver C, Thomassen MJ, Kavuru M, Hammel J, Abu-Soud HM, Erzurum SC (2001) NO chemical events in the human airway during the immediate and late antigen-induced asthmatic response. Proc Natl Acad Sci U S A 98: 2622–2627

    Article  PubMed  CAS  Google Scholar 

  • Edwards G, Weston AH (1995) Pharmacology of the potassium channel openers. Cardiovasc Drugs Ther 9 Suppl 2: 185–193

    Article  Google Scholar 

  • Ellis JL (1997) Role of soluble guanylyl cyclase in the relaxations to a nitric oxide donor and to nonadrenergic nerve stimulation in guinea pig trachea and human bronchus. J Pharmacol Exp Ther 280: 1215–1218

    PubMed  CAS  Google Scholar 

  • Ellis JL, Undem BJ (1992) Inhibition by L-NG-nitro-L-arginine of nonadrenergic-noncholinergic-mediated relaxations of human isolated central and peripheral airway. Am Rev Respir Dis 146: 1543–1547

    PubMed  CAS  Google Scholar 

  • Ellis JL, Undem BJ (1994) Role of cysteinyl-leukotrienes and histamine in mediating intrinsic tone in isolated human bronchi. Am J Respir Crit Care Med 149: 118–122

    PubMed  CAS  Google Scholar 

  • Erjefalt JS, Erjefalt I, Sundler F, Persson CG (1994) Mucosal nitric oxide may tonically suppress airways plasma exudation. Am J Respir Crit Care Med 150: 227–232

    PubMed  CAS  Google Scholar 

  • Faurschou P, Mikkelsen KL, Steffensen I, Franke B (1994) The lack of bronchodilator effect and the short-term safety of cumulative single doses of an inhaled potassium channel opener (bimakalim) in adult patients with mild to moderate bronchial asthma. Pulm Pharmacol 7: 293–297

    Article  PubMed  CAS  Google Scholar 

  • Feder LS, Stelts D, Chapman RW, Manfra D, Crawley Y, Jones H, Minnicozzi M, Fernandez X, Paster T, Egan RW, Kreutner W, Kung TT (1997) Role of nitric oxide on eosinophilic lung inflammation in allergic mice. Am J Respir Cell Mol Biol 17: 436–442

    PubMed  CAS  Google Scholar 

  • Ferreira HH, Bevilacqua E, Gagioti SM, De Luca IM, Zanardo RC, Teixeira CE, Sannomiya P, Antunes E, De Nucci G (1998) Nitric oxide modulates eosinophil infiltration in antigen-induced airway inflammation in rats. Eur J Pharmacol 358: 253–259

    Article  PubMed  CAS  Google Scholar 

  • Fischer A, Canning BJ, Kummer W (1996) Correlation of vasoactive intestinal peptide and nitric oxide synthase with choline acetyltransferase in the airway innervation. Ann N YAcad Sci 805: 717–722

    Article  CAS  Google Scholar 

  • Fischer A, Hoffmann B (1996) Nitric oxide synthase in neurons and nerve fibers of lower airways and in vagal sensory ganglia of man. Correlation with neuropeptides. Am J Respir Crit Care Med 154: 209–216

    Google Scholar 

  • Fischer A, Mundel P, Mayer B, Preissler U, Philippin B, Kummer W (1993) Nitric oxide synthase in guinea pig lower airway innervation. Neurosci Lett 149: 157–160

    Article  PubMed  CAS  Google Scholar 

  • Fluge T, Fabel H, Wagner TO, Schneider B, Forssmann WG (1995) Bronchodilating effects of natriuretic and vasorelaxant peptides compared to salbutamol in asthmatics. Regul Pept 59: 357–370

    Article  PubMed  CAS  Google Scholar 

  • Fluge T, Forssmann WG, Kunkel G, Schneider B, Mentz P, Forssmann K, Barnes PJ, Meyer M (1999) Bronchodilation using combined urodilatin—albuterol administration in asthma: a randomized, double-blind, placebo-controlled trial. Eur J Med Res 4: 411–415

    PubMed  CAS  Google Scholar 

  • Fox AJ, Barnes PJ, Venkatesan P, Belvisi MG (1997) Activation of large conductance potassium channels inhibits the afferent and efferent function of airway sensory nerves in the guinea pig. J Clin Invest 99: 513–519

    Article  PubMed  CAS  Google Scholar 

  • Fujimura M, Kamio Y, Saito M, Hashimoto T, Matsuda T (1995) Bronchodilator and bronchoprotective effects of cilostazol in humans in vivo. Am J Respir Crit Care Med 151: 222–225

    PubMed  CAS  Google Scholar 

  • Gaston B, Drazen JM, Jansen A, Sugarbaker DA, Loscalzo J, Richards W, Stamler JS (1994) Relaxation of human bronchial smooth muscle by S-nitrosothiols in vitro. J Pharmacol Exp Ther 268: 978–984

    PubMed  CAS  Google Scholar 

  • Gaston B, Reilly J, Drazen JM, Fackler J, Ramdev P, Arnelle D, Mullins ME, Sugarbaker DJ, Chee C, Singel DJ,. (1993) Endogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways. Proc Natl Acad Sci U S A 90: 10957–10961

    Article  PubMed  CAS  Google Scholar 

  • Gaston B, Sears S, Woods J, Hunt J, Ponaman M, McMahon T, Stamler JS (1998) Bronchodilator S-nitrosothiol deficiency in asthmatic respiratory failure. Lancet 351: 1317–1319

    Article  PubMed  CAS  Google Scholar 

  • Gourlet P, Vertongen P, Vandermeers A, Vandermeers-Piret MC, Rathe J, De Neef P, Waelbroeck M, Robberecht P (1997) The long-acting vasoactive intestinal polypeptide agonist RO 25–1553 is highly selective of the VIP2 receptor subclass. Peptides 18: 403–408

    Article  PubMed  CAS  Google Scholar 

  • Grissmer S, Nguyen AN, Aiyar J, Hanson DC, Mather RJ, Gutman GA, Karmilowicz MJ, Auperin DD, Chandy KG (1994) Pharmacological characterization of five cloned voltage-gated K+ channels, types Kvl.l, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol Pharmacol 45: 1227–1234

    CAS  Google Scholar 

  • Groneberg DA, Hartmann P, Dinh QT, Fischer A (2001a) Expression and distribution of vasoactive intestinal polypeptide receptor VPAC(2) mRNA in human airways. Lab Invest 81: 749–755

    Article  PubMed  CAS  Google Scholar 

  • Groneberg DA, Springer J, Fischer A (2001b) Vasoactive intestinal polypeptide as mediator of asthma. Pulm Pharmacol Ther 14: 391–401

    Article  PubMed  CAS  Google Scholar 

  • Hamad AM, Johnson SR, Knox AJ (1999) Antiproliferative effects of NO and ANP in cultured human airway smooth muscle. Am J Physiol 277: L910 - L918

    PubMed  CAS  Google Scholar 

  • Hamad AM, Range S, Holland E, Knox AJ (1997) Regulation of cGMP by soluble and particulate guanylyl cyclases in cultured human airway smooth muscle. Am J Physiol 273: L807 - L813

    PubMed  CAS  Google Scholar 

  • Hamid Q, Springall DR, Riveros-Moreno V, Chanez P, Howarth P, Redington A, Bousquet J, Godard P, Holgate S, Polak JM (1993) Induction of nitric oxide synthase in asthma. Lancet Vol 342:-8887

    Google Scholar 

  • Harmar AJ, Arimura A, Gozes I, Journot L, Laburthe M, Pisegna JR, Rawlings SR, Robberecht P, Said SI, Sreedharan SP, Wank SA, Waschek JA (1998) International Union of Pharmacology. XVIII. Nomenclature of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Pharmacol Rev 50: 265270

    Google Scholar 

  • Heim JM, Kiefersauer S, Fulle HJ, Gerzer R (1989) Urodilatin and beta-ANF: binding properties and activation of particulate guanylate cyclase. Biochem Biophys Res Commun 163: 37–41

    Article  PubMed  CAS  Google Scholar 

  • Hobbs AJ (2002) Soluble guanylate cyclase: an old therapeutic target re-visited. Br J Pharmacol 136: 637–640

    Article  PubMed  CAS  Google Scholar 

  • Hogman M, Frostell CG, Hedenstrom H, Hedenstierna G (1993) Inhalation of nitric oxide modulates adult human bronchial tone. Am Rev Respir Dis 148: 1474–1478

    Article  PubMed  CAS  Google Scholar 

  • Hulks G, Mohammed AF, Jardine AG, Connell JM, Thomson NC (1991) Circulating plasma concentrations of atrial natriuretic peptide and catecholamines in response to maximal exercise in normal and asthmatic subjects. Thorax 46: 824–828

    Article  PubMed  CAS  Google Scholar 

  • Ichinose M, Barnes PJ (1990) A potassium channel activator modulates both excitatory noncholinergic and cholinergic neurotransmission in guinea pig airways. J Pharmacol Exp Ther 252: 1207–1212

    PubMed  CAS  Google Scholar 

  • Iijima H, Duguet A, Eum SY, Hamid Q, Eidelman DH (2001) Nitric oxide and protein nitration are eosinophil dependent in allergen-challenged mice. Am J Respir Crit Care Med 163: 1233–1240

    PubMed  CAS  Google Scholar 

  • Janssen LJ (2002) Ionic mechanisms and Ca(2t) regulation in airway smooth muscle contraction: do the data contradict dogma? Am J Physiol Lung Cell Mol Physiol 282: L1161 - L1178

    PubMed  CAS  Google Scholar 

  • Kacmarek RM, Ripple R, Cockrill BA, Bloch KJ, Zapol WM, Johnson DC (1996) Inhaled nitric oxide. A bronchodilator in mild asthmatics with methacholine-induced bronchospasm. Am J Respir Crit Care Med 153: 128–135

    Google Scholar 

  • Kakuyama M, Ahluwalia A, Rodrigo J, Valiance P (1999) Cholinergic contraction is altered in nNOS knockouts. Cooperative modulation of neural bronchoconstriction by nNOS and COX. Am J Respir Crit Care Med 160: 2072–2078

    Google Scholar 

  • Kallstrom BL, Waldeck B (2001) Bronchodilating properties of the VIP receptor agonist Ro 25–1553 compared to those of formoterol on the guinea-pig isolated trachea. Eur J Pharmacol 430: 335–340

    Article  PubMed  CAS  Google Scholar 

  • Kharitonov SA, O’Connor BJ, Evans DJ, Barnes PJ (1995) Allergen-induced late asthmatic reactions are associated with elevation of exhaled nitric oxide. Am J Respir Crit Care Med 151: 1894–1899

    PubMed  CAS  Google Scholar 

  • Kharitonov SA, Yates D, Robbins RA, Logan-Sinclair R, Shinebourne EA, Barnes PJ (1994) Increased nitric oxide in exhaled air of asthmatic patients. Lancet 343: 133135

    Google Scholar 

  • Kidney JC, Fuller RW, Worsdell YM, Lavender EA, Chung KF, Barnes PJ (1993) Effect of an oral potassium channel activator, BRL 38227, on airway function and responsiveness in asthmatic patients: comparison with oral salbutamol. Thorax 48: 130–133

    Article  PubMed  CAS  Google Scholar 

  • Kinhult J, Andersson JA, Uddman R, Stjarne P, Cardell LO (2000) Pituitary adenylate cyclase-activating peptide 38 a potent endogenously produced dilator of human airways. Eur Respir J 15: 243–247

    Article  PubMed  CAS  Google Scholar 

  • Koarai A, Ichinose M, Sugiura H, Yamagata S, Hattori T, Shirato K (2000) Allergic airway hyperresponsiveness and eosinophil infiltration is reduced by a selective iNOS inhibitor, 1400 W, in mice. Pulm Pharmacol Ther 13: 267–275

    Article  CAS  Google Scholar 

  • Kobzik L, Bredt DS, Lowenstein CJ, Drazen J, Gaston B, Sugarbaker D, Stamler JS (1993) Nitric oxide synthase in human and rat lung: immunocytochemical and histochemical localization. Am J Respir Cell Mol Biol 9: 371–377

    PubMed  CAS  Google Scholar 

  • Kume H, Hall IP, Washabau RJ, Takagi K, Kotlikoff MI (1994) Beta-adrenergic agonists regulate KCa channels in airway smooth muscle by cAMP-dependent and -independent mechanisms. J Clin Invest 93: 371–379

    Article  PubMed  CAS  Google Scholar 

  • Laitinen A, Partanen M, Hervonen A, Pelto-Huikko M, Laitinen LA (1985) VIP like immunoreactive nerves in human respiratory tract. Light and electron microscopic study. Histochemistry 82: 313–319

    Google Scholar 

  • Martinez FD, Graves PE, Baldini M, Solomon S, Erickson R (1997) Association between genetic polymorphisms of the beta2-adrenoceptor and response to albuterol in children with and without a history of wheezing. J Clin Invest 100: 3184–3188

    Article  PubMed  CAS  Google Scholar 

  • McAlpine LG, Hulks G, Thomson NC (1992) Effect of atrial natriuretic peptide given by intravenous infusion on bronchoconstriction induced by ultrasonically nebulized distilled water (fog). Am Rev Respir Dis 146: 912–915

    PubMed  CAS  Google Scholar 

  • Miura M, Belvisi MG, Stretton CD, Yacoub MH, Barnes PJ (1992a) Role of K+ channels in the modulation of cholinergic neural responses in guinea-pig and human airways. J Physiol 455: 1–15

    PubMed  CAS  Google Scholar 

  • Miura M, Belvisi MG, Stretton CD, Yacoub MH, Barnes PJ (1992b) Role of potassium channels in bronchodilator responses in human airways. Am Rev Respir Dis 146: 132–136

    PubMed  CAS  Google Scholar 

  • Moya MP, Gow AJ, McMahon TJ, Toone EJ, Cheifetz IM, Goldberg RN, Stamler JS (2001) S-nitrosothiol repletion by an inhaled gas regulates pulmonary function. Proc Natl Acad Sci U S A 98: 5792–5797

    Article  PubMed  CAS  Google Scholar 

  • Muller-Schweinitzer E, Fozard JR (1997) SCA 40: studies of the relaxant effects on cryopreserved human airway and vascular smooth muscle. Br J Pharmacol 120: 1241–1248

    Article  PubMed  CAS  Google Scholar 

  • Myou S, Fujimura M, Kamio Y, Ishiura Y, Tachibana H, Hirose T, Hashimoto T, Matsuda T (1999) Bronchodilator effect of inhaled olprinone, a phosphodiesterase 3 inhibitor, in asthmatic patients. Am J Respir Crit Care Med 160: 817–820

    PubMed  CAS  Google Scholar 

  • Naline E, Bardou M, Devillier P, Molimard M, Dumas M, Chalon P, Manara L, Advenier C (2000) Inhibition by SR 59119A of isoprenaline-, forskolin-and VIP-induced relaxation of human isolated bronchi. Pulm Pharmacol Ther 13: 167–174

    Article  PubMed  CAS  Google Scholar 

  • Nicole P, Lins L, Rouyer-Fessard C, Drouot C, Fulcrand P, Thomas A, Couvineau A, Martinez J, Brasseur R, Laburthe M (2000) Identification of key residues for interaction of vasoactive intestinal peptide with human VPAC1 and VPAC2 receptors and development of a highly selective VPAC1 receptor agonist. Alanine scanning and molecular modeling of the peptide. J Biol Chem 275: 24003–24012

    Google Scholar 

  • Nohr D, Eiden LE, Weihe E (1995) Coexpression of vasoactive intestinal peptide, calcitonin gene-related peptide and substance P immunoreactivity in parasympathetic neurons of the rhesus monkey lung. Neurosci Lett 199: 25–28

    Article  PubMed  CAS  Google Scholar 

  • O’Donnell M, Garippa RJ, Rinaldi N, Selig WM, Simko B, Renzetti L, Tannu SA, Wasserman MA, Welton A, Bolin DR (1994a) Ro 25–1553: a novel, long-acting vasoactive intestinal peptide agonist. Part I: In vitro and in vivo bronchodilator studies. J Pharmacol Exp Ther 270: 1282–1288

    Google Scholar 

  • O’Donnell M, Garippa RJ, Rinaldi N, Selig WM, Tocker JE, Tannu SA, Wasserman MA, Welton A, Bolin DR (1994b) Ro 25–1553: a novel, long-acting vasoactive intestinal peptide agonist. Part II: Effect on in vitro and in vivo models of pulmonary anaphylaxis. J Pharmacol Exp Ther 270: 1289–1294

    Google Scholar 

  • Oonuma H, Iwasawa K, Iida H, Nagata T, Imuta H, Morita Y, Yamamoto K, Nagai R, Ornata M, Nakajima T (2002) Inward rectifier K(+) current in human bronchial smooth muscle cells: inhibition with antisense oligonucleotides targeted to Kir2.1 mRNA. Am J Respir Cell Mol Biol 26: 371–379

    PubMed  CAS  Google Scholar 

  • Palmer JB, Cuss FM, Barnes PJ (1986) VIP and PHM and their role in nonadrenergic inhibitory responses in isolated human airways. J Appl Physiol 61: 1322–1328

    PubMed  CAS  Google Scholar 

  • Patel HJ, Giembycz MA, Keeling JE, Barnes PJ, Belvisi MG (1998) Inhibition of cholinergic neurotransmission in guinea pig trachea by NS1619, a putative activator of large-conductance, calcium-activated potassium channels. J Pharmacol Exp Ther 286: 952958

    Google Scholar 

  • Pelaia G, Gallelli L, Vatrella A, Grembiale RD, Maselli R, De Sarro GB, Marsico SA (2002) Potential role of potassium channel openers in the treatment of asthma and chronic obstructive pulmonary disease. Life Sci 70: 977–990

    Article  PubMed  CAS  Google Scholar 

  • Perreault T, Gutkowska J (1995) Role of atrial natriuretic factor in lung physiology and pathology. Am J Respir Crit Care Med 151: 226–242

    PubMed  CAS  Google Scholar 

  • Poggioli R, Benelli A, Arletti R, Cavazzuti E, Bertolini A (1999) Antitussive effect of K+ channel openers. Eur J Pharmacol 371: 39–42

    Article  PubMed  CAS  Google Scholar 

  • Potter LR, Hunter T (2001) Guanylyl cyclase-linked natriuretic peptide receptors: structure and regulation. J Biol Chem 276: 6057–6060

    Article  PubMed  CAS  Google Scholar 

  • Qian Y, Naline E, Karlsson JA, Raeburn D, Advenier C (1993) Effects of rolipram and siguazodan on the human isolated bronchus and their interaction with isoprenaline and sodium nitroprusside. Br J Pharmacol 109: 774–778

    Article  PubMed  CAS  Google Scholar 

  • Rabe KF, Tenor H, Dent G, Schudt C, Liebig S, Magnussen H (1993) Phosphodiesterase isozymes modulating inherent tone in human airways: identification and characterization. Am J Physiol 264: L458 - L464

    PubMed  CAS  Google Scholar 

  • Ricciardolo FL, Geppetti P, Mistretta A, Nadel JA, Sapienza MA, Bellofiore S, Di Maria GU (1996) Randomised double-blind placebo-controlled study of the effect of inhibition of nitric oxide synthesis in bradykinin-induced asthma. Lancet 348: 374–377

    Article  PubMed  CAS  Google Scholar 

  • Robberecht P, Waelbroeck M, De Neef P, Camus JC, Coy DH, Christophe J (1988) Pharmacological characterization of VIP receptors in human lung membranes. Peptides 9: 339–345

    Article  PubMed  CAS  Google Scholar 

  • Said, S. I., 1998, Antiinflammatory actions of VIP in lungs and airways in Proinflamma- tory and Antiinflammatory Peptides: Said, S. I., Ed., Marcel Dekker, New York.

    Google Scholar 

  • Saleh D, Ernst P, Lim S, Barnes PJ, Giaid A (1998) Increased formation of the potent oxidant peroxynitrite in the airways of asthmatic patients is associated with induction of nitric oxide synthase: effect of inhaled glucocorticoid. FASEB J 12: 929–937

    PubMed  CAS  Google Scholar 

  • Sanna A, Kurtansky A, Venter C, Stanescu D (1994) Bronchodilator effect of inhaled nitric oxide in healthy men. Am J Respir Crit Care Med 150: 1702–1704

    PubMed  CAS  Google Scholar 

  • Sardina, M, Daussogne C, Del Soldato P (2002) New NO-releasing compounds for the treatment of inflammatory airway diseases. XIVth World Congress of Pharmacology [New Drugs for Respiratory Diseases, San Diego 3rd-5th July].

    Google Scholar 

  • Schmidt DT, Ruhlmann E, Waldeck B, Branscheid D, Luts A, Sundler F, Rabe KF (2001) The effect of the vasoactive intestinal polypeptide agonist Ro 25–1553 on induced tone in isolated human airways and pulmonary artery. Naunyn Schmiedebergs Arch Pharmacol 364: 314–320

    Article  PubMed  CAS  Google Scholar 

  • Schmidt DT, Watson N, Dent G, Ruhlmann E, Branscheid D, Magnussen H, Rabe KF (2000) The effect of selective and non-selective phosphodiesterase inhibitors on allergen-and leukotriene C(4)-induced contractions in passively sensitized human airways. Br J Pharmacol 131: 1607–1618

    Article  PubMed  CAS  Google Scholar 

  • Schultz HD, Gardner DG, Deschepper CF, Coleridge HM, Coleridge JC (1988) Vagal C-fiber blockade abolishes sympathetic inhibition by atrial natriuretic factor. Am J Physiol 255: R6–13

    PubMed  CAS  Google Scholar 

  • Sears MR (2001) Short-acting beta-agonist research: a perspective. 1997. Can Respir J 8: 349–355

    PubMed  CAS  Google Scholar 

  • Seino S (1999) ATP-sensitive potassium channels: a model of heteromultimeric potassium channel/receptor assemblies. Annu Rev Physiol 61: 337–362

    Article  PubMed  CAS  Google Scholar 

  • Sharara AM, Hijazi M, Tarawneh M, Ind PW (1998) Nebulized glyceryl trinitrate exerts acute bronchodilator effects in patients with acute bronchial asthma. Pulm Pharmacol Ther 11: 65–70

    Article  PubMed  CAS  Google Scholar 

  • Shaul PW, North AJ, Wu LC, Wells LB, Brannon TS, Lau KS, Michel T, Margraf LR, Star RA (1994) Endothelial nitric oxide synthase is expressed in cultured human bronchiolar epithelium. J Clin Invest 94: 2231–2236

    Article  PubMed  CAS  Google Scholar 

  • Sim JH, Yang DK, Kim YC, Park SJ, Kang TM, So I, Kim KW (2002) ATP-sensitive K(+) channels composed of Kir6.1 and SUR2B subunits in guinea pig gastric myocytes. Am J Physiol Gastrointest Liver Physiol 282: G137 - G144

    PubMed  CAS  Google Scholar 

  • Snetkov VA, Hirst SJ, Twort CH, Ward JP (1995) Potassium currents in human freshly isolated bronchial smooth muscle cells. Br J Pharmacol 115: 1117–1125

    Article  PubMed  CAS  Google Scholar 

  • Snetkov VA, Hirst SJ, Ward JP (1996) Ion channels in freshly isolated and cultured human bronchial smooth muscle cells. Exp Physiol 81: 791–804

    PubMed  CAS  Google Scholar 

  • Snetkov VA, Ward JP (1999) Ion currents in smooth muscle cells from human small bronchioles: presence of an inward rectifier K+ current and three types of large conductance K+ channel. Exp Physiol 84: 835–8460

    Article  PubMed  CAS  Google Scholar 

  • Sreedharan SP, Huang JX, Cheung MC, Goetzl EJ (1995) Structure, expression, and chromosomal localization of the type I human vasoactive intestinal peptide receptor gene. Proc Natl Acad Sci U S A 92: 2939–2943

    Article  PubMed  CAS  Google Scholar 

  • Tam EK, Franconi GM, Nadel JA, Caughey GH (1990) Protease inhibitors potentiate smooth muscle relaxation induced by vasoactive intestinal peptide in isolated human bronchi. Am J Respir Cell Mol Biol 2: 449–452

    PubMed  CAS  Google Scholar 

  • Taylor DA, McGrath JL, O’Connor BJ, Barnes PJ (1998a) Allergen-induced early and late asthmatic responses are not affected by inhibition of endogenous nitric oxide. Am J Respir Crit Care Med 158: 99–106

    PubMed  CAS  Google Scholar 

  • Taylor DA, McGrath JL, Orr LM, Barnes PJ, O’Connor BJ (1998b) Effect of endogenous nitric oxide inhibition on airway responsiveness to histamine and adenosine-5’monophosphate in asthma. Thorax 53: 483–489

    Article  PubMed  CAS  Google Scholar 

  • Teramoto N, Nakashima T, Ito Y (2000) Properties and pharmacological modification of ATP-sensitive K(+) channels in cat tracheal myocytes. Br J Pharmacol 130: 625–635

    Article  PubMed  CAS  Google Scholar 

  • Thomassen MJ, Raychaudhuri B, Dweik RA, Farver C, Buhrow L, Malur A, Connors MJ, Drazba J, Hammel J, Erzurum SC, Kavuru MS (1999) Nitric oxide regulation of asthmatic airway inflammation with segmental allergen challenge. J Allergy Clin Immunol 104: 1174–1182

    Article  PubMed  CAS  Google Scholar 

  • Torphy TJ, Undem BJ, Cieslinski LB, Luttmann MA, Reeves ML, Hay DW (1993) Identification, characterization and functional role of phosphodiesterase isozymes in human airway smooth muscle. J Pharmacol Exp Ther 265: 1213–1223

    PubMed  CAS  Google Scholar 

  • Trifilieff A, Fujitani Y, Mentz F, Dugas B, Fuentes M, Bertrand C (2000) Inducible nitric oxide synthase inhibitors suppress airway inflammation in mice through down-regulation of chemokine expression. J Immunol 165: 1526–1533

    PubMed  CAS  Google Scholar 

  • Turner PJ, Maggs JR, Foreman JC (2000) Induction by inhibitors of nitric oxide synthase of hyperresponsiveness in the human nasal airway. Br J Pharmacol 131: 363–369

    Article  PubMed  CAS  Google Scholar 

  • Ward JK, Barnes PJ, Springall DR, Abelli L, Tadjkarimi S, Yacoub MH, Polak JM, Belvisi MG (1995a) Distribution of human i-NANC bronchodilator and nitric oxide-immunoreactive nerves. Am J Respir Cell Mol Biol 13: 175–184

    PubMed  CAS  Google Scholar 

  • Ward JK, Barnes PJ, Tadjkarimi S, Yacoub MH, Belvisi MG (1995b) Evidence for the involvement of cGMP in neural bronchodilator responses in humal trachea. J Physiol 483 (Pt 2): 525–536

    PubMed  CAS  Google Scholar 

  • Wei Y, Mojsov S (1996) Tissue specific expression of different human receptor types for pituitary adenylate cyclase activating polypeptide and vasoactive intestinal polypeptide: implications for their role in human physiology. J Neuroendocrinol 8: 811–817

    Article  PubMed  CAS  Google Scholar 

  • Williams AJ, Lee TH, Cochrane GM, Hopkirk A, Vyse T, Chiew F, Lavender E, Richards DH, Owen S, Stone P,. (1990) Attenuation of nocturnal asthma by cromakalim. Lancet 336: 334–336

    Article  PubMed  CAS  Google Scholar 

  • Xia M, Sreedharan SP, Bolin DR, Gaufo GO, Goetzl EJ (1997) Novel cyclic peptide agonist of high potency and selectivity for the type II vasoactive intestinal peptide receptor. J Pharmacol Exp Ther 281: 629–633

    PubMed  CAS  Google Scholar 

  • Xiong Y, Karupiah G, Hogan SP, Foster SP, Ramsay AJ (1999) Inhibition of allergic airway inflammation in mice lacking nitric oxide synthase 2. J Immunol 162: 445–452

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. The Sackler Institute of Pulmonary Pharmacology, GKT School of Biomedical Science, Guy’s Campus, King’s College London, 5th floor Hodgkin Building, London, SE1 1UL, UK

    D. Spina

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  1. D. Spina
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  1. Sackler Institute of Pulmonary Pharmacology, GKT School of Biomedical Sciences, 5th Floor, Hodgkin Building, Guy’s Campus, SE1 1UL, London, UK

    Clive P. Page

  2. National Heart & Lung Institute, Department of Thoracic Medicine, Imperial College, Dovehouse Street, SW3 6LY, London, UK

    Peter J. Barnes

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© 2004 Springer-Verlag Berlin Heidelberg

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Spina, D. (2004). New Bronchodilator Drugs. In: Page, C.P., Barnes, P.J. (eds) Pharmacology and Therapeutics of Asthma and COPD. Handbook of Experimental Pharmacology, vol 161. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-09264-4_6

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  • DOI: https://doi.org/10.1007/978-3-662-09264-4_6

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  • Print ISBN: 978-3-642-05590-4

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