Agonist efficacy and receptor desensitization: From partial truths to a fuller picture

British Journal of Pharmacology

Volumn 158, Issue 1, 2009, Pages 165-168

  Charlton, Steven J ^a  

^a Novartis Institutes of Biomedical Research   (United Kingdom)

Author keywords

Adrenaline noradrenaline; Antiasthma copd drugs; Drug receptor mechanisms; Molecular pharmacology; Pulmonary and respiratory pharmacology; Receptors

Indexed keywords

BETA 2 ADRENERGIC RECEPTOR; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; CYCLIC AMP; FORMOTEROL; SALMETEROL;

DRUG EFFICACY; HUMAN; INTERNALIZATION; NONHUMAN; NOTE; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RECEPTOR DOWN REGULATION; RECEPTOR OCCUPANCY;

ADRENERGIC AGONISTS; ANIMALS; HUMANS; RECEPTORS, ADRENERGIC, BETA-2;

EID: 69249213484     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2009.00352.x     Document Type: Note

References (39)

1. Aziz I, Tan KS, Hall IP, Devlin MM, Lipworth BJ (1998). Subsensitivity to bronchoprotection against adenosine monophosphate challenge following regular once-daily formoterol. Eur Respir J 12 (3 580 584.
2. Battram C, Charlton SJ, Cuenoud B, Dowling MR, Fairhurst RA, Farr D et al. (2006). In vitro and in vivo pharmacological characterization of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2- one (indacaterol), a novel inhaled beta(2) adrenoceptor agonist with a 24-h duration of action. J Pharmacol Exp Ther 317 (2 762 770.
3. Bhagat R, Kalra S, Swystun VA, Cockcroft DW (1995). Rapid onset of tolerance to the bronchoprotective effect of salmeterol. Chest 108 (5 1235 1239.
4. Black JW, Leff P (1983). Operational models of pharmacological agonism. Proc R Soc Lond B Biol Sci 220 (1219 141 162.
5. Bleecker ER, Yancey SW, Baitinger LA, Edwards LD, Klotsman M, Anderson WH et al. (2006). Salmeterol response is not affected by beta2-adrenergic receptor genotype in subjects with persistent asthma. J Allergy Clin Immunol 118 (4 809 816.
6. Booth H, Bish R, Walters J, Whitehead F, Walters EH (1996). Salmeterol tachyphylaxis in steroid treated asthmatic subjects. Thorax 51 (11 1100 1104.
7. Chong LK, Peachell PT (1999). Beta-adrenoceptor reserve in human lung: a comparison between airway smooth muscle and mast cells. Eur J Pharmacol 378 (1 115 122.
8. Clark RB, Knoll BJ, Barber R (1999). Partial agonists and G protein-coupled receptor desensitization. Trends Pharmacol Sci 20 (7 279 286.
9. Donohue JF, van Noord JA, Bateman ED, Langley SJ, Lee A, Witek TJ Jr. et al. (2002). A 6-month, placebo-controlled study comparing lung function and health status changes in COPD patients treated with tiotropium or salmeterol. Chest 122 (1 47 55.
10. Donohue JF, Menjoge S, Kesten S (2003). Tolerance to bronchodilating effects of salmeterol in COPD. Respir Med 97 (9 1014 1020.
11. Drotar DE, Davis EE, Cockcroft DW (1998). Tolerance to the bronchoprotective effect of salmeterol 12 h after starting twice daily treatment. Ann Allergy Asthma Immunol 80 (1 31 34.
12. Düringer C, Grundström G, Gürcan E, Dainty IA, Lawson M, Korn SH et al. (2009). Agonist-specific patterns of (2-adrenoceptor responses in human airway cells during prolonged exposure. Br J Pharmacol 158 : 169 179.
13. Fisher SK, Snider RM (1987). Differential receptor occupancy requirements for muscarinic cholinergic stimulation of inositol lipid hydrolysis in brain and in neuroblastomas. Mol Pharmacol 32 : 81 90.
14. FitzGerald JM, Chapman KR, Della Cioppa G, Stubbing D, Fairbarn MS, Till MD et al. (1999). Sustained bronchoprotection, bronchodilatation, 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 (3 Pt 1 427 435.
15. Giannini D, Di Franco A, Bacci E, Dente FL, Bartoli ML, Vagaggini B et al. (2001). Tolerance to the protective effect of salmeterol on allergen challenge can be partially restored by the withdrawal of salmeterol regular treatment. Chest 119 : 1671 1675.
16. Giembycz MA, Kaur M, Leigh R, Newton R (2008). A Holy Grail of asthma management: toward understanding how long-acting beta2-adrenoceptor agonists enhance the clinical efficacy of inhaled corticosteroids. Br J Pharmacol 153 : 1090 1104.
17. Hanania NA, Sharafkhaneh A, Barber R, Dickey BF (2002). Beta-agonist intrinsic efficacy: measurement and clinical significance. Am J Respir Crit Care Med 165 : 1353 1358.
18. Hanania NA, Kalberg C, Yates J, Emmett A, Horstman D, Knobil K (2005). The bronchodilator response to salmeterol is maintained with regular, long-term use in patients with COPD. Pulm Pharmacol Ther 18 (1 19 22.
19. Haney S, Hancox RJ (2005). Rapid onset of tolerance to beta-agonist bronchodilation. Respir Med 99 (5 566 571.
20. January B, Seibold A, Whaley B, Hipkin RW, Lin D, Schonbrunn A et al. (1997). beta2-adrenergic receptor desensitization, internalization, and phosphorylation in response to full and partial agonists. J Biol Chem 272 (38 23871 23879.
21. January B, Seibold A, Allal C, Whaley BS, Knoll BJ, Moore RH et al. (1998). Salmeterol-induced desensitization, internalization and phosphorylation of the human beta2-adrenoceptor. Br J Pharmacol 123 (4 701 711.
22. Johnson M (1998). The beta-adrenoceptor. Am J Respir Crit Care Med 158 (5 Pt 3 S146 S153.
23. Johnson M (2006). Molecular mechanisms of beta(2)-adrenergic receptor function, response, and regulation. J Allergy Clin Immunol 117 (1 18 24.
24. Kenakin T (2005). New concepts in drug discovery: collateral efficacy and permissive antagonism. Nat Rev Drug Discov 4 (11 919 927.
25. Kenakin T (2006). A Pharmacological Primer. Theory, Application and Methods, 2nd edn. Elsevier Inc Burlington, MA.
26. Knox AJ, Mortimer K (2008). Combining inhaled glucocorticoids and long acting beta2-adrenoceptor agonists in asthma and COPD. Br J Pharmacol 153 : 1085 1086.
27. Lipworth B, Tan S, Devlin M, Aiken T, Baker R, Hendrick D (1998). Effects of treatment with formoterol on bronchoprotection against methacholine. Am J Med 104 (5 431 438.
28. Lipworth BJ (1997). Airway subsensitivity with long-acting beta 2-agonists. Is there cause for concern? Drug Saf 16 (5 295 308.
29. McDonnell J, Latif ML, Rees ES, Bevan NJ, Hill SJ (1998). Influence of receptor number on the stimulation by salmeterol of gene transcription in CHO-K1 cells transfected with the human beta2-adrenoceptor. Br J Pharmacol 125 (4 717 726.
30. McGraw DW, Liggett SB (1997). Heterogeneity in beta-adrenergic receptor kinase expression in the lung accounts for cell-specific desensitization of the beta2-adrenergic receptor. J Biol Chem 272 (11 7338 7344.
31. Moore RH, Millman EE, Godines V, Hanania NA, Tran TM, Peng H et al. (2007). Salmeterol stimulation dissociates beta2-adrenergic receptor phosphorylation and internalization. Am J Respir Cell Mol Biol 36 (2 254 261.
32. Newnham DM, Grove A, McDevitt DG, Lipworth BJ (1995). Subsensitivity of bronchodilator and systemic beta 2 adrenoceptor responses after regular twice daily treatment with eformoterol dry powder in asthmatic patients. Thorax 50 (5 497 504.
33. van Rossum J, Ariens EJ (1962). Receptor-reserve and threshold-phenomena. II. Theories on drug-action and a quantitative approach to spare receptors and threshold values. Arch Int Pharmacodyn Ther 136 : 385 413.
34. Scola AM, Chong LK, Suvarna SK, Chess-Williams R, Peachell PT (2004). Desensitisation of mast cell beta2-adrenoceptor-mediated responses by salmeterol and formoterol. Br J Pharmacol 141 (1 163 171.
35. Scola AM, Loxham M, Charlton SJ, Peachell PT (2009). The long-acting beta2-adrenoceptor agonist, indacaterol, inhibits IgE-dependent responses of human lung mast cells. Br J Pharmacol 158 : 267 276.
36. Steffensen I, Faurschou P, Riska H, Rostrup J, Wegener T (1995). Inhaled formoterol dry powder in the treatment of patients with reversible obstructive airway disease. A 3-month, placebo-controlled comparison of the efficacy and safety of formoterol and salbutamol, followed by a 12-month trial with formoterol. Allergy 50 (8 657 663.
37. Sutherland ER (2004). Outpatient treatment of chronic obstructive pulmonary disease: comparisons with asthma. J Allergy Clin Immunol 114 : 715 724.
38. Tsagaraki V, Amfilochiou A, Markantonis SL (2006). Evidence of tachyphylaxis associated with salmeterol treatment of chronic obstructive pulmonary disease patients. Int J Clin Pract 60 (4 415 421.
39. Ullman A, Hedner J, Svedmyr N (1990). Inhaled salmeterol and salbutamol in asthmatic patients. An evaluation of asthma symptoms and the possible development of tachyphylaxis. Am Rev Respir Dis 142 (3 571 575.