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Current issues with β2-adrenoceptor agonists

Pharmacology and molecular and cellular mechanisms

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Abstract

β2-Adrenoceptors are widely, almost ubiquitously, expressed. Activation of these receptors on bronchial smooth muscle by short-and long-acting β2-adrenoceptor agonists causes bronchodilation. Here, the β2-adrenoceptor is linked by the G protein, Gs, to adenylyl cyclase, which increases cyclic adenosine monophosphate (cAMP), thus activating protein kinase A, which affects calcium levels and reduces the efficiency of myosin light-chain kinase, causing relaxation. Activation also entrains numerous acute and longer term downregulation responses affecting the number, location, and net efficiency of signaling of the receptor. Synthetic β2-agonists are all “partial agonists,” incompletely, able to optimally stimulate cAMP signal transduction. However, compared with some cells (such as mast cells) involved in exercise-induced ashtma induction, airway smooth muscle is privileged in that transduction efficiency is intrinsically high and the tissue is very resistant to complete downregulation. Glucocorticosteroids have broadly beneficial interactions with β2-adrenoceptors. Researchers have recently discovered that the β2-adrenoceptor may function as a homodimer and that it can form heterodimers with both the β1- β3-adrenoceptors, and possibly other, receptors. This further complicates interpretation of the effect of β2-adrenoceptor polymorphisms, but it is unknown whether this occurs in humans in vivo. Researchers have known for some time that strong contraction involving receptors coupled to the Gq G protein (e.g., cholinergic and leukotriene receptors via negative biochemical crosstalk), virus infection (via uncoupling), and inflammation (via kinases) can impair relaxation. Most recently, researchers have discovered that the β2-adrenoceptor can also send potentially adverse signals after “atypical coupling” to Gq rather than Gs. The clinical implications of these uncouplings, crosstalk and atypical coupling possibilities are not well-understood.

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References

  1. Carstairs J. R., Nimmo, A. J., and Barnes, P. J. (1985). Atitoradiographic visualization of beta-adrenoceptor subtypes in human lung. Am. Rev. Respir. Dis. 132, 541–547.

    PubMed  CAS  Google Scholar 

  2. Mak, J. C., Nishikawa, M., Haddad, E. B., et al. (1996), Localisation and expression of beta-adrenoceptor subtype mRNAs in human lung. Eur. J. Pharmacol. 302, 215–221.

    Article  PubMed  CAS  Google Scholar 

  3. Anderson, G. P. (1993) Long acting inhaled beta-adrenoceptor agonists the comparative pharmacology of formoterol and salmeterol. Agents Actions Suppl, 43, 253–269.

    PubMed  CAS  Google Scholar 

  4. Anderson, G. P. (1993), Formoterol: pharmacology, molecular basis of agonism, and mechanism of long duration of a highly potent and selective beta 2-adrenoceptor agonist bronchodilator. Life Sci. 52, 2145–2160.

    Article  PubMed  CAS  Google Scholar 

  5. O'Donnell, S. R. and Anderson, G. P. (1995), The effects of formoterol on plasma exudation produced by a localized acute inflammatory response to bradykinin in the tracheal mucosa of rats in vivo. Br. J. Pharmacol. 116, 1571–1576.

    PubMed  Google Scholar 

  6. Bowden, J. J., Anderson, G. P., Lefevre, P. M., Sulakvelidze, I., and McDonald, D. M., (1997). Characterization of tolerance to the anti-leakage effect of formoterol in rat airways. Eur. J. Pharmacol. 338, 83–87.

    Article  PubMed  CAS  Google Scholar 

  7. Anderson, G. P. (2000), Interactions between corticosteroids and beta-adrenergic agonists in asthma disease induction, progression, and exacerbation. Am. J. Respir. Crit. Care Med. 161, S188-S196.

    PubMed  CAS  Google Scholar 

  8. Barnes, P. J. (1993), Beta-adrenoceptors on smooth muscle, nerves and inflammatory cells. Life Sci. 52, 2101–2109.

    Article  PubMed  CAS  Google Scholar 

  9. Johnson, M., Butchers, P. R., Coleman, R. A., et al. (1993), The pharmacology of salmeterol. Life Sci. 52, 2131–2143.

    Article  PubMed  CAS  Google Scholar 

  10. Kips, J. C., O'Connor B. J., Inman, M. D., Svensson, K., Pauwels, R. A., and O'Byrne, P. M. (2000), A long-term study of the antiinflammatory effect of low-dose budesonide plus formoterol versus highdose budesonide in asthma. Am. J. Respir. Crit. Care Med. 161, 996–1001.

    PubMed  CAS  Google Scholar 

  11. Maneechotesuwan, K., Essilfie-Quaye, S., Meah, S., et al. (2005), Formoterol attenuates neutrophilic airway inflammation in asthma. Chest 128, 1936–1942.

    Article  PubMed  CAS  Google Scholar 

  12. Roth, M., Johnson, P. R., Rudiger, J. J. et al. (2002), Interaction between glucocorticoids and beta 2 agonists on bronchial airway smooth muscle cells through synchronised cellular signalling. Lancet 360, 1293–1299.

    Article  PubMed  CAS  Google Scholar 

  13. Edwards, M. R., Johnson, M. W., and Johnston, S. L. (2006). Combination therapy: synergistic suppression of virus induced chemokines in airway epithelial cells. Am. J. Respir. Cell Mol. Biol. 34, 616–624.

    Article  PubMed  CAS  Google Scholar 

  14. Kruse, M., Rosenkranz, B., Dobson, C., Ayre, G., and Horowitz, A. (2005) Safety and tolerability of high-dose formoterol (Aerolizer) and salbutamol (pMDI) in patients with mild/moderate, persistent asthma. Pulm. Pharmacol. Ther. 18, 229–234.

    Article  PubMed  CAS  Google Scholar 

  15. Goldkorn, A., Diotto, P., Burgess, C., et al. (2004), The pulmonary and extra-pulmonary effects of high-dose formoterol in COPD: a comparison with salbutamol. Respirology 9, 102–108.

    Article  PubMed  Google Scholar 

  16. Burgess, C., Ayson, M., Rajasingham, S, Crane, J., Della Cioppa, G., and Till, M. D. (1998). The extrapulmonary effects of increasing doses of formoterol in patients with asthma. Eur. J. Clin. Pharmacol. 54, 141–147.

    Article  PubMed  CAS  Google Scholar 

  17. Cazzola, M., Imperatore, F., Salzillo, A., et al. (1998), Cardiac effects of formoterol and salmeterol in patients suffering from COPD with preexisting cardiac arrhythmias and hypoxemia. Chest 114, 411–415.

    PubMed  CAS  Google Scholar 

  18. Nelson, H. S. (2006), Is there a problem with inhaled long-acting beta-adrenergic agonists. J. Allergy Clin. Immunol. 117, 3–16.

    Article  PubMed  CAS  Google Scholar 

  19. Martinez, F. D. (2005), Satety of long-acting beta-agonists—an urgent need to clear the air. N. Engl. J. Med. 353, 2637–2639.

    Article  PubMed  CAS  Google Scholar 

  20. Taylor, D. R., Drazen, J. M., Herbison, G. P., Yandava, C. N., Hancox, R. J., and Town, G. I. (2000), Asthma exacerbations during long term beta agonist use: influence of beta(2) adrenoceptor polymorphism. Thorax 55, 762–767.

    Article  PubMed  CAS  Google Scholar 

  21. Israel, E., Drazen, J. M., Liggett, S. B. et al (2000), The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to regular use of albuterol in asthma. Am. J. Respir. Crit. Care Med. 162, 75–80.

    PubMed  CAS  Google Scholar 

  22. Ramsdale, E. H., Klinse, P. A., Contovnick L. S., Hargreave, F. E., and O'Byrne, P. M. (1991), Prolonged protection against methacholine-induced bronchoconstriction by the inhaled beta 2-agonist formoterol. Am. Rev. Respir. Dis. 143, 998–1001.

    PubMed  CAS  Google Scholar 

  23. Pauwels, R. A., Lofdahl, C. G., Postma, D. S., et al. (1997), Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. N. Engl. J. Med. 337, 1405–1411.

    Article  PubMed  CAS  Google Scholar 

  24. O'Connor, R. D., Rosenzweig, J. R., Stanford, R. H., et al. (2005), Asthma-related exacerbations, therapy switching, and therapy discontinuation: a comparison of 3 commonly used controller regimens. Ann. Allergy Asthma Immunol. 95, 535–540.

    Article  PubMed  Google Scholar 

  25. Cullum, V. A., Farmer, J. B., Jack, D., and Levy, G. P. (1969), Salbutamol: a new, selective beta-adrenoceptive receptor stimulant. Br. J. Pharmacol. 35, 141–151.

    PubMed  CAS  Google Scholar 

  26. Jack, D. (1991), The 1990 Lilly Prize Lecture. A way of looking at agonism and antagonism: lessons from salbutamol, salmeterol and other beta-adrenoceptor agenists. Br. J. Clin. Pharmacol. 31, 501–514.

    PubMed  CAS  Google Scholar 

  27. Tomioka, K., Yamada, T., and Ida, H. (1981), Anti-allergic activities of the beta-adrenoceptor stimulant formoterol (BD 40A). Arch. Int. Pharmacodyn. Ther. 250, 279–292.

    PubMed  CAS  Google Scholar 

  28. Mita, H. and Shida, T. (1983), Anti-allergic activity of formoterol, a new beta-adrenoceptor stimulant, and salbutamol in human leukocytes and human lung tissue. Allergy 38, 547–552.

    Article  PubMed  CAS  Google Scholar 

  29. Tomioka, K., Yamada, T., and Tachikawa, S. (1984), Effects of formoterol (BD 40A), a beta-adrenoceptor stimulant, on isolated guinea-pig lung parenchymal strips and antigen-induced SRS-A release in rats. Arch. Int. Pharmacodyn. Ther. 267, 91–102.

    PubMed  CAS  Google Scholar 

  30. Green, S. A., Spasoff, A. P., Coleman, R. A., Johnson, M., and Liggett, S. B. (1996). Sustained activation of a G protein-coupled receptor via “anchored” agonist binding. Molecular localization of the salmeterol exosite within the 2-adrenergic receptor. J. Biol. Chem. 271, 24,029–24,035.

    CAS  Google Scholar 

  31. Anderson, G. P., Linden, A., Rabe, K. F. (1994), Why are long-acting beta-adrenoceptor agonists long-acting?. Eur. Respir. J. 7, 569–578.

    Article  PubMed  CAS  Google Scholar 

  32. Guhan, A. R., Cooper, S., Oborne, J., Lewis, S., Bennett, J. and Tattersfield, A. E. (2000). Systemic effects of formoterol and salmeterol: a dose-response comparison in healthy subjects. Thorax 55, 650–656.

    Article  PubMed  CAS  Google Scholar 

  33. Bennett, J. and Tattersfield, A. E. (1997). Several studies have shown salmeterol to be more potent than salbutamol for systemic effects. S. M. J. 315, 121.

    CAS  Google Scholar 

  34. Barnes, P. J. and Pride, N. B. (1983). Dose-response curves to inhaled beta-adrenoceptor agonists in normal and asthmatic subjects. Br. J. Clin. Pharmacol. 15, 677–682.

    PubMed  CAS  Google Scholar 

  35. Molimard, M., Naliné, E., Zhang, Y., Le Gres, V., Begaud, B, and Advenier, C. (1998), Long- and short-acting beta2 adrenoceptor agonists: interactions in human contracted bronchi. Eur. Respir. J. 11, 583–588.

    PubMed  CAS  Google Scholar 

  36. Nightingale, J. A., Rogers, D. F., and Barnes, P. J. (1999), Differential effect of formoterol on adenosine monophosphate and histamine reactivity in asthma. Am. J. Respir. Crit. Care Med. 159, 1786–1790.

    PubMed  CAS  Google Scholar 

  37. Freddolino, P. L., Kalani, M. Y., Vaidehi, N., et al. (2004), Predicted 3D structure for the human beta 2 adrenergic receptor and its binding site for agonists and antagonists. Proc. Natl. Acad. Sci. USA 101, 2736–2741.

    Article  PubMed  CAS  Google Scholar 

  38. Dixon, R. A., Sigal, I. S., Rands, E., et al. (1987). Ligand binding to the beta-adrenergic receptor involves its rhodopsin-like core. Nature 326, 73–77.

    Article  PubMed  CAS  Google Scholar 

  39. Rands, E., Candelore, M. R., Cheung, A. H., Hill, W. S., Strader, C. D., and Dixon, R. A. (1990). Mutational analysis of beta-adrenergic receptor glycosylation. J. Biol. Chem. 265, 10,759–10,764.

    CAS  Google Scholar 

  40. O'Dowd, B. F., Hnatowich, M., Caron, M. G., Lefkowitz, R. J., and Bouvier, M. (1989), Palmitoylation of the human beta 2-adrenergic receptor. Mutation of Cys341 in the carboxyl tail leads to an uncoupled nonpalmitoylated form of the receptor. J. Biol. Chem. 264, 7564–7569.

    PubMed  Google Scholar 

  41. Moffett, S., Adam, L., Bonin, H., Loisel, T. P., Bouvier, M., and Mouillac, B. (1996), Palmitoylated cysteine 341 modulates phosphorylation of the beta2-adrenergic receptor by the cAMP-dependent protein kinase. J. Biol. Chem. 271, 21,490–21,497.

    Article  CAS  Google Scholar 

  42. Moffett, S., Rousseau, G., Lagace, M., and Bouvier, M. (2001), The palmitoylation state of the beta(2)-adrenergic receptor regulates the synergistic action of cyclic AMP-dependent protein kinase and beta-adrenergic receptor kinase involved in its phosphorylation and desensitization. J. Neurochem. 76, 269–279.

    Article  PubMed  CAS  Google Scholar 

  43. Strader, C. D., Sigal, I. S., Register, R. B., Candelore, M. R., Rands, E., and Dixon, R. A. (1987), Identification of residues required for ligand binding to the beta-adrenergic receptor. Proc. Natl. Acad. Sci. USA 84, 4384–4388.

    Article  PubMed  CAS  Google Scholar 

  44. Dixon, R. A., Sigal, I. S., Candelore, M. R., et al. (1987) Structural features required for ligand binding to the beta-adrenergic receptor. Embo. J. 6, 3269–3275.

    PubMed  CAS  Google Scholar 

  45. Truong-Tran, A. Q., Grosser, D., Ruffin, R. E., Murgia, C., and Zalewski, P. D. (2003), Apoptosis in the normal and inflamed airway epithelium: role of zinc in epithelial protection and procaspase-3 regulation. Biochem. Pharmacol. 66, 1459–1468.

    Article  PubMed  CAS  Google Scholar 

  46. Swaminath, G., Lee, T. W., and Kobilka, B. (2003), Identification of an allosteric binding site for Zn2+ on the beta2 adrenergic receptor. J. Biol. Chem. 278, 352–356.

    Article  PubMed  CAS  Google Scholar 

  47. Green, S. A., Rathz, D. A., Schuster, A. J., and Liggett, S. B. (2001), The Ile164 beta(2)-adrenoceptor polymorphism alters salmeterol exosite binding and conventional agonist coupling to G(s). Eur. J. Pharmacol. 421, 141–147.

    Article  PubMed  CAS  Google Scholar 

  48. Salahpour, A., Angers, S., Mercier, J. F., Lagace, M., Marullo, S., and Bouvier, M. (2004), Homodimerization of the beta2-adrenergic receptor as a prerequisite for cell surface targeting. J. Biol. Chem. 279, 33,390–33,397.

    Article  CAS  Google Scholar 

  49. Hebert, T. E., Loisel, T. P., Adam, L., Ethier, N., Onge, S. S., and Bouvier, M. (1998), Functional rescue of a constitutively desensitized beta2AR through receptor dimerization. Biochem. J. 330 (Pt 1), 287–293.

    PubMed  CAS  Google Scholar 

  50. Zhu, W. Z., Chakir, K., Zhang, S., et al. (2005), Heterodimerization of betal- and beta2-adrenergic receptor subtypes optimizes beta-adrenergic modulation of cardiac contractility. Circ. Res. 97, 244–251.

    Article  PubMed  CAS  Google Scholar 

  51. Breit, A., Lagace, M., and Bouvier, M. (2004), Hetero-oligomerization between beta2- and beta3-adrenergic receptors generates a beta-adrenergic signaling unit with distinct functional properties. J. Biol. Chem. 279, 28,756–28,765.

    Article  CAS  Google Scholar 

  52. Mercier, J. F., Salahpour, A., Angers, S., Breit, A., and Bouvier, M. (2002), Quantitative assessment of beta 1- and beta 2-adrenergic receptor homoand heterodimerization by bioluminescence resonance energy transfer. J. Biol. Chem. 277, 44,925–44,931.

    Article  CAS  Google Scholar 

  53. Lavoie, C., Mercier, J. F., Salahpour A., et al. (2002), Beta 1/beta 2-adrenergic receptor heterodimerization regulates beta 2-adrenergic receptor internalization and ERK signaling efficacy. J. Biol. Chem. 277, 35,402–35,410.

    Article  CAS  Google Scholar 

  54. Salahpour, A., Bonin, H., Bhalla, S., Petaja-Repo, U., and Bouvier, M. (2003), Biochemical characterization of beta2-adrenergic receptor dimers and oligomers. Biol. Chem. 384, 117–123.

    Article  PubMed  CAS  Google Scholar 

  55. Spicuzza, L., Belvisi, M. G., Birrell, M. A., Barnes, P. J., Hele, D. J., and Giembycz, M. A. (2001), Evidence that the anti-spasmogenic effect of the beta-adrenoceptor agonist, isoprenaline, on guinea-pig trachealis is not mediated by cyclic AMP-dependent protein kinase. Br. J. Pharmacol. 133, 1201–1212.

    Article  PubMed  CAS  Google Scholar 

  56. Hall, R. A., Ostedgaard, L. S., Premont, R. T., et al. (1998), A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins. Proc. Natl. Acad. Sci. USA 95, 8496–8501.

    Article  PubMed  CAS  Google Scholar 

  57. Hall, R. A., Premont, R. T., Chow, C. W., et al. (1998), The beta2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange. Nature 392, 626–630.

    Article  PubMed  CAS  Google Scholar 

  58. Cook, S. J., Small, R. C., Berry, J. L., Chiu, P., Downing, S. J., and Foster, R. W. (1993), Beta-adrenoceptor subtypes and the opening of plasmalemmal K(+)-channels in trachealis muscle: electrophysiological and mechanical studies in guinea-pig tissue. Br. J. Pharmacol. 109, 1140–1148.

    PubMed  CAS  Google Scholar 

  59. Shenoy, S. K., McDonald, P. H., Kohout, T. A., and Lefkowitz, R. J. (2001), Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic receptor and beta-arrestin. Science 294, 1307–1313.

    Article  PubMed  CAS  Google Scholar 

  60. Lavine, N., Ethier, N., Oak, J. N., et al. (2002), G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase. J. Biol. Chem. 277, 46,010–46,019.

    Article  CAS  Google Scholar 

  61. Iyer, V., Tran, T. M., Foster, E., Dai, W., Clark, R. B., and Knoll, B. J. (2006), Differential phosphorylation and dephosphorylation of beta(2)-adrenoceptor sites Ser 262 and Ser355,356. Br. J. Pharmacol. 147, 249–259.

    Article  PubMed  CAS  Google Scholar 

  62. FitzCerald, J. M., Chapman, K. R., Della Cloppa, G., et al. (1999), Sustained bronchoprotection, bronchodilation, and symptom control during regular formoterol use in asthma of moderate or greater severity. The Canadian FO/OD1 Study Group. J. Allergy Clin. Immunol. 103, 427–435.

    Article  Google Scholar 

  63. Aziz, I., Tan, K. S., Hall, I. P., Devlin, M. M., and Lipworth, B. J. (1998), Subsensitivity to bronchoprotection against adenosine monophosphate challenge following regular once-daily formoterol. Eur. Respir. J. 12, 580–584.

    Article  PubMed  CAS  Google Scholar 

  64. Lee, D. K., Currie, G. P., Hall, I. P., Lima, J. J., and Lipworth, B. J. (2004), The arginine-16 beta2-adrenoceptor polymorphism predisposes to bronchoprotective subsensitivity in patients treated with formoterol and salmeterol. Br. J. Clin. Pharmacol. 57, 68–75.

    Article  PubMed  CAS  Google Scholar 

  65. Tan, K. S., Grove, A., McLean, A., Gnosspelius, Y., Hall, I. P., and Lipworth, B. J. (1997), Systemic corticosteriod rapidly reverses bronchodilator subsensitivity induced by formoterol in asthmatic patients. Am. J. Respir. Crit. Care Med. 156, 28–35.

    PubMed  CAS  Google Scholar 

  66. Lipworth, B. J. and Aziz, I. (2000), Bronchodilator response to albuterol after regular formoterol and effects of acute corticosteroid administration. Chest 117, 156–162.

    Article  PubMed  CAS  Google Scholar 

  67. Boulet, L. P., Cartier, A., Milet, J., Cote, J., Male, J. L., and Laviolette, M. (1998), Tolerance to the protective effects of salmeterol on methacholine-induced bronchoconstriction: influence of inhaled corticosteroids. Eur. Respir. J. 11, 1091–1097.

    Article  PubMed  CAS  Google Scholar 

  68. Nishikawa, M., Mak, J. C., and Barnes, P. J. (1996), Effect of short- and long-acting beta 2-adrenoceptor agonists on pulmonary beta 2-adrenoceptor expression in human lung. Eur. J. Pharmacol. 318, 123–129.

    Article  PubMed  CAS  Google Scholar 

  69. Lemoine, H., Overlack, C., Kohl, A., Worth, H., and Reinhardt, D. (1992), Formoterol, fenoterol, and salbutamol as partial agonists for relaxation of maximally contracted guinea pig tracheae: comparison of relaxation with receptor binding. Lung 170, 163–180.

    Article  PubMed  CAS  Google Scholar 

  70. Lemoine, H. and Overlack, C. (1992), Highly potent beta-2 sympathomimetics convert to less potent partial agonists as relaxants of guinea pig tracheae maximally contracted by carbachol. Comparison of relaxation with receptor binding and adenylate cyclase stimulation. J. Pharmacol. Exp. Ther. 261, 258–270.

    PubMed  CAS  Google Scholar 

  71. Campbell, P. T., Hnatowich, M., O'Dowd, B. F., Caron, M. G., Lefkowitz, R. J., and Hausdorff, W. P. (1991), Mutations of the human beta 2-adrenergic receptor that impair coupling to Gs interfere with receptor down-regulation but not sequestration. Mol. Pharmacol. 39, 192–198.

    PubMed  CAS  Google Scholar 

  72. Jockers, R., Angers, S., Da Silva, A., et al. (1999), Beta(2)-adrenergic receptor down-regulation. Evidence for a pathway that does not require endocytosis. J. Biol. Chem. 274, 28,900–28,908.

    Article  CAS  Google Scholar 

  73. Finney, P. A., Belvisi, M. G., Donnelly, L. E., et al. (2000), Albuterol-induced downregulation of G-alpha aecounts for pulmonary beta(2)-adrenoceptor desensitization in vivo. J. Clin. Invest. 106, 125–135.

    Article  PubMed  CAS  Google Scholar 

  74. Van Amsterdam, R. G., Meurs, H., Ten Berge, R. E., Veninga, N. C., Brouwer, F., and Zaagsma, J. (1990), Role of phosphoinositide metabolism in human bronchial smooth muscle contraction and in functional antagonism by beta-adrenoceptor agonists. Am. Rev. Respir. Dis. 142, 1124–1128.

    PubMed  Google Scholar 

  75. Wills-Karp, M., Uchida, Y., Lee, J. Y., Jinot, J., Hirata, A., and Hirata, F. (1993), Organ culture with proinflammatory cytokines reproduces impairment of the beta-adrenoceptor-mediated relaxation in tracheas of a guinea pig antigen model. Am. J. Respir. Cell Mol. Biol. 8, 153–159.

    PubMed  CAS  Google Scholar 

  76. Bai, T. R., Mak, J. C., and Barnes, P. J. (1992), A comparison of beta-adrenergic receptors and in vitro relaxant responses to isoproterenol in asthmatic airway smooth muscle. Am. J. Respir. Cell Mol. Biol. 6, 647–651.

    PubMed  CAS  Google Scholar 

  77. Bai, T. R. (1991), Abnormalities in airway smooth muscle in fatal asthma. A comparison between trachea and bronchus. Am. Rev. Respir. Dis. 143, 441–443.

    PubMed  CAS  Google Scholar 

  78. McGraw, D. W., Almoosa, K. F., Paul, R. J., Kobilka, B. K., and Liggett, S. B. (2003), Antithetic regulation by beta-adrenergic receptors of Gq receptor signaling via phospholipase C underlies the airway beta-agonist paradox. J. Clin. Invest. 112, 610–626.

    Article  CAS  Google Scholar 

  79. Caliaerts-Vegh, Z., Evans, K. L., Dudekula, N., et al. (2004), Effects of acute and chronic administration of beta-adrenoceptor ligands on airway function in a murine model of asthma. Proc. Natl. Acad. Sci. USA 101, 4948–4953.

    Article  CAS  Google Scholar 

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    Gary P. Anderson

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Anderson, G.P. Current issues with β2-adrenoceptor agonists. Clinic Rev Allerg Immunol 31, 119–130 (2006). https://doi.org/10.1385/CRIAI:31:2:119

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