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Possible mechanisms of the bronchoprotective effect of chronic beta blocker treatment in a murine model of asthma
Author(s) -
Lin Rui,
Parra Sergio,
Chan Becky,
Frieske Joanna,
Syed Arsalan,
Knoll Brian J.,
Bond Richard A.
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1169-b
In a previous study, we showed that the beneficial effect of chronic treatment with nadolol, a β‐adrenoceptor (β‐AR) inverse agonist, on airway function in a murine model of asthma was associated with increased β‐AR density. However, dexamethasone and guanadrel, which also increased β‐AR density in our animal model of asthma, did not show any protective effect on methacholine induced bronchoconstriction. The bronchoprotective effect of nadolol chronic treatment was attenuated when combined with reserpine, an analog of guanadrel which depletes endogenous catecholamines. Therefore, airway function is not simply due to the upregulation of β‐AR density. In order to investigate other possible mechanisms responsible for the bronchoprotective effect of nadolol chronic treatment, we measured the effect of chronic nadolol treatment on the expression of Gs, Gi, and Gq proteins, and phosphodiesterase 4D (PDE4D). Chronic nadolol treatment decreased the expression of Gi and PDE4D, but did not change the expression of Gs and Gq. The decrease in PDE4D and Gi may enhance cAMP accumulation via β‐AR activation. Supported by Sandler program for Asthma Research