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Agonist-specific patterns of beta(2)-adrenoceptor responses in human airway cells during prolonged exposure.

Düringer, Caroline LU ; Grundström, Gunilla; Gürcan, Eylem LU ; Dainty, Ian A; Lawson, Mandy; Korn, Solange H; Jerre, Anders; Håkansson, Hanna Falk; Wieslander, Elisabet and Hägerbrand, Karin LU , et al. (2009) In British Journal of Pharmacology 158. p.169-179
Abstract
Background and purpose: beta(2)-Adrenoceptor agonists (beta(2)-agonists) are important bronchodilators used in the treatment of asthma and chronic obstructive pulmonary disease. At the molecular level, beta(2)-adrenergic agonist stimulation induces desensitization of the beta(2)-adrenoceptor. In this study, we have examined the relationships between initial effect and subsequent reduction of responsiveness to restimulation for a panel of beta(2)-agonists in cellular and in vitro tissue models. Experimental approach: beta(2)-Adrenoceptor-induced responses and subsequent loss of receptor responsiveness were studied in primary human airway smooth muscle cells and bronchial epithelial cells by measuring cAMP production. Receptor responsiveness... (More)
Background and purpose: beta(2)-Adrenoceptor agonists (beta(2)-agonists) are important bronchodilators used in the treatment of asthma and chronic obstructive pulmonary disease. At the molecular level, beta(2)-adrenergic agonist stimulation induces desensitization of the beta(2)-adrenoceptor. In this study, we have examined the relationships between initial effect and subsequent reduction of responsiveness to restimulation for a panel of beta(2)-agonists in cellular and in vitro tissue models. Experimental approach: beta(2)-Adrenoceptor-induced responses and subsequent loss of receptor responsiveness were studied in primary human airway smooth muscle cells and bronchial epithelial cells by measuring cAMP production. Receptor responsiveness was compared at equi-effective concentrations, either after continuous incubation for 24 h or after a 1 h pulse exposure followed by a 23 h washout. Key findings were confirmed in guinea pig tracheal preparations in vitro. Key results: There were differences in the reduction of receptor responsiveness in human airway cells and in vitro guinea pig trachea by a panel of beta(2)-agonists. When restimulation occurred immediately after continuous incubation, loss of responsiveness correlated with initial effect for all agonists. After the 1 h pulse exposure, differences between agonists emerged, for example isoprenaline and formoterol induced the least reduction of responsiveness. High lipophilicity was, to some extent, predictive of loss of responsiveness, but other factors appeared to be involved in determining the relationships between effect and subsequent loss of responsiveness for individual agonists. Conclusions and implications: There were clear differences in the ability of different beta(2) agonists to induce loss of receptor responsiveness at equi-effective concentrations. (Less)
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British Journal of Pharmacology
volume
158
pages
169 - 179
publisher
The British Pharmacological Society
external identifiers
  • wos:000269315700016
  • pmid:19558544
  • scopus:69249202368
ISSN
1476-5381
DOI
10.1111/j.1476-5381.2009.00262.x
language
English
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yes
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b16855c6-b1ca-410d-938b-3ff838bc1fb6 (old id 1433823)
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http://www.ncbi.nlm.nih.gov/pubmed/19558544?dopt=Abstract
date added to LUP
2009-07-06 11:48:42
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2017-08-13 04:38:20
@article{b16855c6-b1ca-410d-938b-3ff838bc1fb6,
  abstract     = {Background and purpose: beta(2)-Adrenoceptor agonists (beta(2)-agonists) are important bronchodilators used in the treatment of asthma and chronic obstructive pulmonary disease. At the molecular level, beta(2)-adrenergic agonist stimulation induces desensitization of the beta(2)-adrenoceptor. In this study, we have examined the relationships between initial effect and subsequent reduction of responsiveness to restimulation for a panel of beta(2)-agonists in cellular and in vitro tissue models. Experimental approach: beta(2)-Adrenoceptor-induced responses and subsequent loss of receptor responsiveness were studied in primary human airway smooth muscle cells and bronchial epithelial cells by measuring cAMP production. Receptor responsiveness was compared at equi-effective concentrations, either after continuous incubation for 24 h or after a 1 h pulse exposure followed by a 23 h washout. Key findings were confirmed in guinea pig tracheal preparations in vitro. Key results: There were differences in the reduction of receptor responsiveness in human airway cells and in vitro guinea pig trachea by a panel of beta(2)-agonists. When restimulation occurred immediately after continuous incubation, loss of responsiveness correlated with initial effect for all agonists. After the 1 h pulse exposure, differences between agonists emerged, for example isoprenaline and formoterol induced the least reduction of responsiveness. High lipophilicity was, to some extent, predictive of loss of responsiveness, but other factors appeared to be involved in determining the relationships between effect and subsequent loss of responsiveness for individual agonists. Conclusions and implications: There were clear differences in the ability of different beta(2) agonists to induce loss of receptor responsiveness at equi-effective concentrations.},
  author       = {Düringer, Caroline and Grundström, Gunilla and Gürcan, Eylem and Dainty, Ian A and Lawson, Mandy and Korn, Solange H and Jerre, Anders and Håkansson, Hanna Falk and Wieslander, Elisabet and Hägerbrand, Karin and Sköld, Carl Magnus and Löfdahl, Magnus and Löfdahl, Claes-Göran and Nicholls, David J and Silberstein, David S},
  issn         = {1476-5381},
  language     = {eng},
  pages        = {169--179},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {Agonist-specific patterns of beta(2)-adrenoceptor responses in human airway cells during prolonged exposure.},
  url          = {http://dx.doi.org/10.1111/j.1476-5381.2009.00262.x},
  volume       = {158},
  year         = {2009},
}