• Joanna S. Thompson Coon
  • Anne E. Tattersfield
Part of the Progress in Inflammation Research book series (PIR)


β2-Adrenoceptor agonists are widely used as bronchodilators and have been used to treat acute attacks of asthma for decades. They can be divided into the very short acting which last 1 to 2 h (e.g. rimiterol), the short-acting such as salbutamol which produce an effect for 4 to 6 h and the newer longer acting β-agonists such as salmeterol and formoterol which maintain bronchodilatation for at least 12 h [1, 2]. β-Agonists antagonise the effects of a wide variety of bronchoconstrictor agents on airway smooth muscle in vitro and in vivo and are thus functional antagonists. The main mechanism by which they cause smooth muscle relaxation involves the cyclic 3′5′ adenosine monophosphate (cAMP) second messenger system which is linked to the β2-adrenoceptor by a coupling G-protein and adenylate cyclase, the effector enzyme [3] (Fig. 1). Cyclic AMP is able to modulate a number of processes which are important in governing the contractile state of the cell [4].


Airway Smooth Muscle Eosinophil Cationic Protein Antigen Challenge Mild Asthma Nedocromil Sodium 
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  1. 1.
    Ullman A and Svedmyr N (1988) Salmeterol, a new long acting inhaled β2-adrenoceptor agonist: comparisons with salbutamol in adult asthmatic patients. Thorax 43: 674–678PubMedCrossRefGoogle Scholar
  2. 2.
    Ringdal N, Derom E, Pauwels R (1995) Onset and duration of action of single doses of formoterol inhaled via Turbuhaler in mild to moderate asthma. Eur Respir J 8: 68SGoogle Scholar
  3. 3.
    Caron M G, Cerione R A, Benovic J L, Strulovici C, Lefkowitz R J, Codina-Salada J, Birnbaumer L (1985) Biochemical characterization of the adrenergic receptors: Affinity labelling, purification and reconstitution studies. Adv Cyclic Nucleotide Protein Phosphorylation Res 19: 1–12PubMedGoogle Scholar
  4. 4.
    Knox AJ, Tattersfield AE (1995) Airway smooth muscle relaxation. Thorax 50: 894–901PubMedCrossRefGoogle Scholar
  5. 5.
    Green SA, Spasoff AP, Coleman RA, Johnson M, Liggett SB (1996) Sustained activation of a G protein coupled receptor via “anchored” agonist binding. Molecular localization of the salmeterol exosite within the β2 adrenergic receptor. J Biol Chem 271: 24029–24035PubMedCrossRefGoogle Scholar
  6. 6.
    Nials AT, Ball DI, Butchers PR, Coleman RA, Humbles AA, Johnson M, Vardey CJ (1994) Formoterol on airway smooth muscle and human lung mast cells: a comparison with salbutamol and salmeterol. Eur J Pharmacol 251: 127–135PubMedCrossRefGoogle Scholar
  7. 7.
    Persson CGA (1993) The action of β-receptors on microvascular endothelium or: Is airways plasma exudation inhibited by β-agonists? Life Sci 52: 2111–2121PubMedCrossRefGoogle Scholar
  8. 8.
    Svensjo E, Persson CGA, Rutili G (1977) Inhibition of bradykinin induced macromolecular leakage from post capillary venules by a β2 adrenoceptor stimulant, terbutaline. Acta Physiol Scand 101: 504–506PubMedCrossRefGoogle Scholar
  9. 9.
    Erjefalt I (1986) Anti-asthma drugs attenuate inflammatory leakage of plasma into airway lumen. Acta Physiol Scand 128: 653–654PubMedCrossRefGoogle Scholar
  10. 10.
    Advenier C, Qian Y, Law Koune J-D, Molimard M, Candenas M-L, Naline E (1992) Formoterol and salbutamol inhibit bradykinin and histamine induced airway microvascular leakage in guinea-pig. Br J Pharmacol 105: 792–798PubMedCrossRefGoogle Scholar
  11. 11.
    Tokuyama K, Lotvall JO, Lofdahl C-G, Barnes PJ, Chung KF (1991) Inhaled formoterol inhibits histamine-induce airflow obstruction and airway microvascular leakage. Eur J Pharmacol 193: 35–39PubMedCrossRefGoogle Scholar
  12. 12.
    Erjefalt I, Persson CGA (1991) Long duration and high potency of anti-exudative effects of formoterol in guinea pig tracheobronchial airways. Am Rev Resp Dis 144: 788–791PubMedCrossRefGoogle Scholar
  13. 13.
    Whelan CJ and Johnson M (1992) Inhibition by salmeterol of increased vascular permeability and granulocyte accumulation in guinea pig lung and skin. Br J Pharmacol 105: 831–838PubMedCrossRefGoogle Scholar
  14. 14.
    Whelan CJ, Johnson M, Vardey CJ (1993) Comparison of the anti-inflammatory properties of formoterol, salbutamol and salmeterol in guinea pig lung and skin. Br J Pharmacol 110: 613–618PubMedCrossRefGoogle Scholar
  15. 15.
    Beets JL and Paul W (1980) Actions of locally administered adrenoceptor agonists on increased plasma protein extravasation and blood flow in guinea-pig skin. Br J Pharmacol 70: 461–467PubMedCrossRefGoogle Scholar
  16. 16.
    Duffey ME, Hainau B, Ho S, Bentzel CJ (1981) Regulation of epithelial tight junction permeability by cyclic AMP. Nature 294: 451–453PubMedCrossRefGoogle Scholar
  17. 17.
    Sulakvelidze I, McDonald DM (1994) Anti-edema action of formoterol in rat trachea does not depend on capsaicin sensitive sensory nerves. Am J Resp Crit Care Med 149: 232–238PubMedGoogle Scholar
  18. 18.
    Butchers PR, Skidmore IF, Vardey CJ, Wheldon A (1980) Characterisation of the receptor mediating the anti-analphylactic effects of β-adrenoceptor agonists in human lung tissue in vitro. Br J Pharmacol 71: 663–667PubMedCrossRefGoogle Scholar
  19. 19.
    Yukawa T, Ukena D, Kroegel C, Chanez P, Dent G, Chung KF, Barnes PJ (1990) Beta-adrenergic receptors on eosinophils. Am Rev Resp Dis 141: 1446–1452PubMedGoogle Scholar
  20. 20.
    Liggett SB (1989) Identification and characterisation of a homogenous population of β2 adrenergic receptors on human alveolar macrophages. Am Rev Resp Dis 139: 552–555PubMedCrossRefGoogle Scholar
  21. 21.
    Williams LT, Snyderman R, Lefkowitz RJ (1976) Identification of β-adrenergic receptors in human lymphocytes by (-)[3H] alprenolol binding. J Allergy Clin Immunol 57: 149–155CrossRefGoogle Scholar
  22. 22.
    Conolly ME, Greenacre JK (1977) The β-adrenoceptor of the human lymphocyte and human lung parenchyma. Br J Pharmacol 59: 17–23PubMedCrossRefGoogle Scholar
  23. 23.
    Bishopric NH, Cohen HJ, Lefkowitz RJ (1980) Beta-adrenergic receptors in lymphocyte sub-populations. J Allergy Clin Immunol 65: 29–33PubMedCrossRefGoogle Scholar
  24. 24.
    Galant SP and Allred SJ (1980) Demonstration of beta-2 adrenergic receptors of high coupling efficiency in human neutrophil sonicates. J Lab Clin Med 96: 15–23PubMedGoogle Scholar
  25. 25.
    Assem ESK, Richter AM (1971) Comparison of in vitro and in vivo inhibition of the anaphylactic mechanism by β-adrenergic stimulants and disodium cromoglycate. Immunology 21: 729–739PubMedGoogle Scholar
  26. 26.
    Church MK, Young KD (1983) The characteristics of inhibition of histamine release from human lung fragments by sodium cromoglycate, salbutamol and chlorpromazine. Br J Pharmacol 78: 671–679PubMedCrossRefGoogle Scholar
  27. 27.
    Church MK, Hiroi J (1987) Inhibition of IgE-dependent histamine release from human dispersed lung mast cells by anti-allergic drugs and salbutamol. Br J Pharmacol 90: 421–429PubMedCrossRefGoogle Scholar
  28. 28.
    Rabe KF, Giembycz MA, Dent G, Perkins RS, Evans P, Barnes PJ (1993) Salmeterol is a competitive antagonist at β-adrenoceptors mediating inhibition of respiratory burst in guinea pig eosinophils. Eur J Pharmacol 231: 305–308PubMedCrossRefGoogle Scholar
  29. 29.
    Busse WW, Sosman JM (1984) Isoproteronol inhibition of isolated human neutrophil function. J Allergy Clin Immunol 73: 404–410PubMedCrossRefGoogle Scholar
  30. 30.
    Mary D, Aussel C, Ferrua B, Fehlmann M (1987) Regulation of interleukin 2 synthesis by cAMP in human T cells. J Immunol 139: 1179–1184PubMedGoogle Scholar
  31. 31.
    Averill LE, Stein RL, Kammer GM (1988) Control of human T-lymphocyte interleukin-2 production by a cAMP dependent pathway. Cell Immunology 115: 88–99CrossRefGoogle Scholar
  32. 32.
    Carlson SL, Trauth K, Brooks WH, Roszman TL (1994) Enhancement of beta-adrenergic-induced cAMP accumulation in activated T-cells. J Cell Physiol 161: 39–48PubMedCrossRefGoogle Scholar
  33. 33.
    Fuller RW, O’Malley G, Baker AJ, Macdermot J (1988) Human alveolar macrophage activation: Inhibition by forskolin but not β-adrenoceptor stimulation or phosphodiesterase inhibition. Pulm Pharmacol 1: 101–106PubMedCrossRefGoogle Scholar
  34. 34.
    Baker AJ, Palmer J, Johnson M, Fuller RW (1994) Inhibitory actions of salmeterol on human airway macrophages and blood monocytes. Eur J Pharmacol 264: 301–306PubMedCrossRefGoogle Scholar
  35. 35.
    Butchers PR, Vardey CJ, Johnson M (1991) Salmeterol a potent and long acting inhibitor of inflammatory mediator release from human lung. Br J Clin Pharmacol 104: 672–676Google Scholar
  36. 36.
    Lau HY, Wong PL, Lai CK, Ho JK (1994) Effects of long acting β2 adrenoceptor agonists on mast cells of rat, guinea pig and human. Int Arch Allergy Immunol 105: 177–180PubMedCrossRefGoogle Scholar
  37. 37.
    Sanjar S, McCabe PJ, Humbles AH (1991) Inhibition by salmeterol of antigen-induced eosinophil accumulation in guinea pig lung. Eur Respir J 4: 200sGoogle Scholar
  38. 38.
    Dowling RB, Rayner CFJ, Rutman A, Jackson AD, Kanthakumar K, Dewar A, Taylor GW, Cole PJ, Johnson M, Wilson R (1997) Effect of salmeterol on Pseudomonas aeruginosa infection of respiratory mucosa. Am J Resp Crit Care Med 155: 327–336PubMedGoogle Scholar
  39. 39.
    Sekut L, Champion BR, Page K, Menius JA, Connolly KM (1995) Anti-inflammatory activity of salmeterol; down regulation of cytokine production. Clin Exp Immunol 99: 461–466PubMedCrossRefGoogle Scholar
  40. 40.
    Baker AJ, Fuller RW (1990) Anti-inflammatory effect of salmeterol on human alveolar macrophages. Am Rev Resp Dis 141: A394Google Scholar
  41. 41.
    Pin I, Gibson PG, Kolendowicz R, Girgis-Garbado A, Denburg JA, Hargreave FE, Dolovich J (1992) Use of induced sputum cell counts to investigate airway inflammation in asthma. Thorax 47: 25–29PubMedCrossRefGoogle Scholar
  42. 42.
    Laitinen LA, Laitinen A, Haahtela T (1992) A comparative study of the effects of an inhaled corticosteroid, budesonide, and a β2-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: A randomised, double-blind, parallel-group controlled trial. J Allergy Clin Immunol 90: 32–42PubMedCrossRefGoogle Scholar
  43. 43.
    Manolitsas ND, Wang J, Devalia JL, Trigg CJ, McAulay AE, Davies RJ (1995) Regular albuterol, nedocromil sodium and bronchial inflammation in asthma. Am J Resp Crit Care Med 151: 1925–1930PubMedGoogle Scholar
  44. 44.
    Evans DW, Salome CM, King GG, Rimmer SJ, Seale JP, Woolcock AJ (1997) Effect of regular inhaled salbutamol on airway responsiveness and airway inflammation in rhinitic non-asthmatic subjects. Thorax 52: 136–142PubMedCrossRefGoogle Scholar
  45. 45.
    Di Lorenzo G, Morici G, Norrito F, Mansueto P, Melluso M, D’Ambrosio FP, Sangiorgi GB (1995) Comparison of the effects of salmeterol and salbutamol on clinical activity and eosinophil cationic protein serum levels during the pollen season in atopic asthmatics. Clin Exp Allergy 25: 951–956PubMedCrossRefGoogle Scholar
  46. 46.
    Twentyman OP, Sams VR, Holgate ST (1993) Albuterol and nedocromil sodium affect airway and leukocyte responses to allergen. Am Rev Respir Dis 147: 1425–1430PubMedGoogle Scholar
  47. 47.
    Howarth PH, Durham SR, Lee TH, Kay AB, Church MK, Holgate ST (1985) Influence of albuterol, cromolyn sodium and ipratropium bromide on the airway and circulating mediator responses to allergen bronchial provocation in asthma. Am Rev Resp Dis 132: 986–992PubMedGoogle Scholar
  48. 48.
    Dahl R, Pedersen B, Venge P (1991) Bronchoalveolar lavage studies. Eur Resp Rev 1: 272–275Google Scholar
  49. 49.
    Roberts JA, Bradding P, Walls AF, Holgate ST, Howarth PH (1992) The effect of salmeterol xinafoate therapy on lavage findings in asthma. Am Rev Resp Dis 145: A418Google Scholar
  50. 50.
    Roberts JA, Bradding P, Walls AF, Britten KM, Wilson S, Holgate ST, Howarth PH (1992) The influence of salmeterol xinafoate on mucosal inflammation in asthma. Am Rev Resp Dis 145: A418Google Scholar
  51. 51.
    Gratziou C, Roberts J A, Bradding P, Holgate S T, Howarth P H (1992) The influence of the long acting β-agonist salmeterol xinafoate on T-lymphocyte lavage populations and activation status in asthma. Am Rev Resp Dis 145: A67Google Scholar
  52. 52.
    Gardiner PV, Ward C, Booth H, Allison A, Hendrick DJ, Walters EH (1994) Effect of eight weeks of treatment with salmeterol on bronchoalveolar lavage inflammatory indices in asthmatics. Am J Resp Crit Care Med 150: 1006–1011PubMedGoogle Scholar
  53. 53.
    Wong BJO, Dolovich J, Ramsdale HE, O’Byrne PM, Gontovnick L, Denburg JA, Hargreave FE (1992) Formoterol compared with beclomethasone and placebo on allergen-induced asthmatic responses. Am Rev Resp Dis 146: 1156–1160PubMedGoogle Scholar
  54. 54.
    Pedersen B, Dahl R, Larsen BB, Venge P (1993) The effect of salmeterol on the early and late phase reaction to bronchial allergen and postchallenge variation in bronchial reactivity, blood eosinophils, serum eosinophil cationic protein and serum eosinophil protein X. Allergy 48: 377–382PubMedCrossRefGoogle Scholar
  55. 55.
    Weersink E J M, Postma D S, Aalbers R, De Monchy J G R (1994) Early and late asthmatic reaction after allergen challenge. Resp Med 88: 103–114CrossRefGoogle Scholar
  56. 56.
    Pizzichini M M M, Kidney J C, Wong B J O, Morris M M, Efthimiadis A, Dolovich J, Hargreave F E (1996) Effect of salmeterol compared with beclomethasone on allergen-induced asthmatic and inflammatory responses. Eur Respir J 9: 449–455PubMedCrossRefGoogle Scholar
  57. 57.
    Twentyman O P, Finnerty J P, Holgate S T (1991) The inhibitory effect of nebulized albuterol on the early and late asthmatic reactions and increase in airway responsiveness provoked by inhaled allergen in asthma. Am Rev Resp Dis 144: 782–787PubMedCrossRefGoogle Scholar
  58. 58.
    Twentyman OP, Finnerty JP, Harris A, Palmer J, Holgate ST (1990) Protection against allergen induced asthma by salmeterol. Lancet 336: 1338–1342PubMedCrossRefGoogle Scholar
  59. 59.
    Sears M, Taylor DR, Print CG, Lake DC, Li Q, Flannery EM, Yates DM, Lucas MK, Herbison GP (1990) Regular inhaled β-agonist treatment in bronchial asthma. Lancet 336: 1391–1396PubMedCrossRefGoogle Scholar
  60. 60.
    Pearlman DS, Chervinsky P, LaForce C, Seltzer JM, Southern DL, Kemp JP, Dockhorn RJ, Grossman J, Liddle RF, Yancey SW, Cocchetto DM, Alexander WJ, Van As A (1992) A comparison of salmeterol with albuterol in the treatment of mild-to-moderate asthma. New Engl J Med 327: 1420–1425PubMedCrossRefGoogle Scholar
  61. 61.
    D’Alonzo GE, Nathan RA, Henochowicz S, Morris RJ, Ratner P, Rennard SI (1994) Salmeterol xinafoate as maintenance therapy with albuterol in patients with asthma. JAMA 271: 1412–1416PubMedCrossRefGoogle Scholar
  62. 62.
    Drazen JM, Israel E, Boushey HA, Chinchilli VM, Fahy JV, Fish JE, Lazarus SC, Lemanske RF, Martin RJ, Peters SP, Sorkness C, Szefler SJ (1996) Comparison with regularly scheduled with as-needed use of albuterol in mild asthma. New Engl J Med 335: 841–847PubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel AG 1999

Authors and Affiliations

  • Joanna S. Thompson Coon
    • 1
  • Anne E. Tattersfield
    • 1
  1. 1.Division of Respiratory MedicineCity HospitalNottinghamUK

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