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Mechanisms of impaired beta-adrenoceptor-induced airway relaxation by interleukin-1beta in vivo in the rat.

https://arctichealth.org/en/permalink/ahliterature11157
Source
J Clin Invest. 1996 Oct 15;98(8):1780-7
Publication Type
Article
Date
Oct-15-1996
Author
H. Koto
J C Mak
E B Haddad
W B Xu
M. Salmon
P J Barnes
K F Chung
Author Affiliation
Thoracic Medicine, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Source
J Clin Invest. 1996 Oct 15;98(8):1780-7
Date
Oct-15-1996
Language
English
Publication Type
Article
Keywords
Animals
Autoradiography
Bronchi - drug effects - physiology
Cyclic AMP - metabolism
Forskolin - pharmacology
GTP-Binding Proteins - analysis
Interleukin-1 - pharmacology
Isoproterenol - pharmacology
Muscle Relaxation - drug effects
RNA, Messenger - analysis
Rats
Rats, Inbred BN
Receptors, Adrenergic, beta - analysis - genetics - physiology
Research Support, Non-U.S. Gov't
Trachea - drug effects - physiology
Abstract
We studied the in vivo mechanism of beta-adrenergic receptor (beta-AR) hyporesponsiveness induced by intratracheal instillation of interleukin-1beta (IL-1beta, 500 U) in Brown-Norway rats. Tracheal and bronchial smooth muscle responses were measured under isometric conditions ex vivo. Contractile responses to electrical field stimulation and to carbachol were not altered, but maximal relaxation induced by isoproterenol (10(-6)-10(-5) M) was significantly reduced 24 h after IL-1beta treatment in tracheal tissues and to a lesser extent, in the main bronchi. Radioligand binding using [125I]iodocyanopindolol revealed a 32+/-7% reduction in beta-ARs in lung tissues from IL-1beta-treated rats, without any significant changes in beta2-AR mRNA level measured by Northern blot analysis. Autoradiographic studies also showed significant reduction in beta2-AR in the airways. Isoproterenol-stimulated cyclic AMP accumulation was reduced by IL-1beta at 24 h in trachea and lung tissues. Pertussis toxin reversed this hyporesponsiveness to isoproterenol but not to forskolin in lung tissues. Western blot analysis revealed an IL-1beta-induced increase in Gi(alpha) protein expression. Thus, IL-1beta induces an attenuation of beta-AR-induced airway relaxation through mechanisms involving a reduction in beta-ARs, an increase in Gi(alpha) subunit, and a defect in adenylyl cyclase activity.
PubMed ID
8878428 View in PubMed
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