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Inhibition of Gi/o‐proteins prevents hypoxia‐induced impairment of beta2‐adrenergic signalling in primary rat alveolar epithelial cells
Author(s) -
Baloglu Emel,
Ke Alberto,
Bartsch Peter,
Mairbaurl Heimo
Publication year - 2008
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.22.1_supplement.748.8
Subject(s) - forskolin , adenylyl cyclase , endocrinology , terbutaline , medicine , hypoxia (environmental) , stimulation , receptor , pertussis toxin , reabsorption , biology , chemistry , g protein , organic chemistry , oxygen , asthma , kidney
Hypoxia inhibits lung alveolar reabsorption, whereas β2‐adrenergics stimulate. Hypoxia inhibits β2‐adrenergic signaling in a variety of tissues, but effects on alveolar epithelium are not known. To test this, primary rat alveolar type II cells were isolated, cultured to confluence, and incubated in normoxia or hypoxia (3% O2) for 24 hours. cAMP production was measured as an indicator of receptor function and adenylyl cyclase (AC) activity. Maximal terbutalin stimulated cAMP production was decreased by ∼30% in hypoxia; potency of terbutaline‐stimulation was not affected. However, forskolin‐stimulated AC was not inhibited by hypoxia. Receptor density assessed by ICYP binding in absence and presence of β2‐specific antagonist ICI‐118.551 (100μM) was decreased in hypoxia (−25%). To identify possible contribution of G proteins (Gs, Gi/o) to decrease cAMP production in hypoxia, AII cells were incubated with pertussis toxin (PTX; 0.5ng/ml) for 2 hours in normoxia or hypoxia before stimulation with terbutaline. PTX increased terbutalin‐stimulated cAMP production of hypoxic AII cells to normoxic control values, but did not further increase cAMP production in normoxia. PTX did not affect terbutalin potency. Our data suggest that hypoxia‐induced decrease in β2‐adrenergic signaling results mainly from an increased activity of Gi/o proteins.