Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2004 Jan;57(1):100-4.
doi: 10.1046/j.1365-2125.2003.01978.x.

Acute systemic effects of inhaled salbutamol in asthmatic subjects expressing common homozygous beta2-adrenoceptor haplotypes at positions 16 and 27

Daniel K C Lee  1 , Caroline E Bates, Brian J Lipworth
Affiliations
Clinical Trial

Acute systemic effects of inhaled salbutamol in asthmatic subjects expressing common homozygous beta2-adrenoceptor haplotypes at positions 16 and 27

Daniel K C Lee et al. Br J Clin Pharmacol. 2004 Jan.

Abstract

Aims: The relationship between beta2-adrenoceptor polymorphisms at positions 16 and 27, and the acute systemic beta2-adrenoceptor effects of inhaled salbutamol is unclear. We therefore elected to evaluate the influence of common homozygous beta2-adrenoceptor haplotypes on the acute systemic beta2-adrenoceptor effects following inhaled salbutamol in asthmatic subjects.

Methods: An initial database search of 531 asthmatic subjects identified the two commonest homozygous haplotypes at positions 16 and 27 to be Arg16-Gln27 (12%) and Gly16-Glu27 (19%). After a 1-week washout period where all beta2-adrenoceptor agonists were withdrawn, 16 Caucasian subjects (Arg16-Gln27: n = 8 and Gly16-Glu27: n = 8) were given a single dose of inhaled salbutamol (1200 microg), followed by serial blood sampling for serum potassium, along with measurements of diastolic blood pressure and heart rate, at 5-min intervals for 20 min.

Results: The two groups were well matched for age, sex, FEV1, and inhaled corticosteroid dose. Baseline values for serum potassium, diastolic blood pressure and heart rate were not significantly different comparing Arg16-Gln27 vs Gly16-Glu27. The mean +/- SEM maximum serum potassium change from baseline over 20 min was significantly greater (P = 0.04) for Arg16-Gln27: -0.37 +/- 0.05 mmol l(-1) vs Gly16-Glu27: -0.23 +/- 0.04 mmol l(-1); 95% CI for difference: -0.01 to -0.28 mmol l(-1). The maximum diastolic blood pressure change from baseline over 20 min was significantly greater (P = 0.0008) for Arg16-Gln27: -13 +/- 1 mmHg vs Gly16-Glu27: -4 +/- 2 mmHg; 95% CI for difference: -5, 14 mmHg. There was no significant difference comparing the maximum heart rate change from baseline for Arg16-Gln27: 10 +/- 3 beats min(-1) vs Gly16-Glu27: 10 +/- 3 beats min(-1).

Conclusions: Caucasian asthmatic subjects with the Arg16-Gln27 haplotype exhibited a greater systemic response to inhaled salbutamol, compared with those with the Gly16-Glu27 haplotype. The attenuated beta2-adrenoceptor response in the Gly16-Glu27 haplotype would be in keeping with increased susceptibility to prior down-regulation by endogenous catecholamines.

PubMed Disclaimer

Figures

Figure 1
Figure 1
a)Time profile for the serum potassium as change from baseline, with SEM Arg16-Gln27 (•) and Gly16-Glu27 (○). b) individual data for the maximum potassium change from baseline over 20 min, with mean values depicted as horizontal lines.
Figure 1
Figure 1
a)Time profile for the serum potassium as change from baseline, with SEM Arg16-Gln27 (•) and Gly16-Glu27 (○). b) individual data for the maximum potassium change from baseline over 20 min, with mean values depicted as horizontal lines.
Figure 2
Figure 2
a) Time profile for the diastolic blood pressure as change from baseline, with SEM Arg16-Gln27 (•) and Gly16-Glu27 (○). b) individual data for the maximum diastolic blood pressure change from baseline over 20 min, with mean values depicted as horizontal lines.
Figure 2
Figure 2
a) Time profile for the diastolic blood pressure as change from baseline, with SEM Arg16-Gln27 (•) and Gly16-Glu27 (○). b) individual data for the maximum diastolic blood pressure change from baseline over 20 min, with mean values depicted as horizontal lines.
See this image and copyright information in PMC

References

    1. Green SA, Cole G, Jacinto M, Innis M, Liggett SB. A polymorphism of the human beta2-adrenergic receptor within the fourth transmembrane domain alters ligand binding and functional properties of the receptor. J Biol Chem. 1993;268:23116–23121. - PubMed
    1. Green SA, Turki J, Bejarano P, Hall IP, Liggett SB. Influence of beta2-adrenergic receptor genotypes on signal transduction in human airway smooth muscle cells. Am J Respir Cell Mol Biol. 1995;13:25–33. - PubMed
    1. Liggett SB. The pharmacogenetics of beta2-adrenergic receptors: relevance to asthma. J Allergy Clin Immunol. 2000;105:S487–S492. - PubMed
    1. Drysdale CM, McGraw DW, Stack CB, Stephens JC, Judson RS, Nandabalan K, et al. Complex promoter and coding region beta2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc Natl Acad Sci U S A. 2000;97:10483–10488. - PMC - PubMed
    1. Lipworth BJ, Hall IP, Tan S, Aziz I, Coutie W. Effects of genetic polymorphism on ex vivo and in vivo function of beta2-adrenoceptors in asthmatic patients. Chest. 1999;115:324–328. - PubMed

Publication types