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A‐kinase anchoring proteins (AKAPs) regulate airway smooth muscle secretory function
Author(s) -
Poppinga Wilfred J,
Oldenburger Anouk,
Holtzer Laura J,
Driessen Saskia,
Heijink Irene H,
Maarsingh Harm,
Schmidt Martina
Publication year - 2013
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.27.1_supplement.882.5
Subject(s) - fenoterol , copd , medicine , protein kinase a , phosphodiesterase , kinase , phosphorylation , pharmacology , mapk/erk pathway , microbiology and biotechnology , immunology , chemistry , biology , asthma , enzyme , biochemistry
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease mainly caused by cigarette smoke. Current pharmacotherapy involves β2‐agonists and phosphodiesterase inhibitors. Both drugs elevate cAMP, but relieve a distinct subset of COPD symptoms. This may be mediated by A‐kinase anchoring proteins (AKAPs) that compartmentalize cAMP signaling. Here we studied the role of AKAPs in human airway smooth muscle (ASM) secretory function. Using western blot, radio‐assays for PKA binding (RII overlay) and RT‐qPCR we show that human ASM cells express AKAP5, AKAP8, AKAP9, AKAP12 and ezrin, and that cigarette smoke extract (CSE) decreases AKAP5, AKAP9 and AKAP12 expression. In line, we observed reduced mRNA expression of these AKAPs in lung tissue homogenates of COPD patients compared to healthy controls. Disruption of AKAP functions using st‐Ht31 augmented CSE‐induced IL‐8 release and prevented the inhibitory effect of the β2‐agonist fenoterol on CSE‐induced IL‐8 release. St‐Ht31 also diminished the inhibitory effect of fenoterol on CSE‐induced ERK phosphorylation, but not NFκB activation. Thus, the anti‐inflammatory effect of fenoterol on ASM secretory function is mediated by AKAPs. The reduction of specific AKAPs in COPD may disrupt compartmentalized cAMP and thereby affect pharmacotherapy. Supported by Dutch Asthma Foundation grant 3.2.11.015 and a Rosalind Franklin Fellowship.