In vitro hypoxia impairs 2-adrenergic receptor signaling in primary rat alveolar epithelial cells

Baloğlu E, Ke A, Abu-Taha IH, Bärtsch P, Mairbäurl H. In vitro hypoxia impairs 2-adrenergic receptor signaling in primary rat alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol 296: L500 –L509, 2009. First published December 19, 2008; doi:10.1152/ajplung.90390.2008.—Hypoxia inhibits 2-adrenergic receptor ( 2-AR) signaling in a variety of tissues, but effects in alveolar epithelium are unclear. We therefore examined the effect of 24 h of hypoxia on 2-AR function in primary rat alveolar epithelial [alveolar type II (ATII)] cells. ATII cells were isolated, cultured to confluence, and incubated in normoxia or hypoxia (3% O2) for 24 h. Hypoxia decreased maximal terbutaline-stimulated cAMP production by 37%; potency of terbutaline was not affected. Reoxygenation (3 h) reversed this effect. Density of 2-AR assessed by ( )-[I]iodocyanopindolol binding was decreased in hypoxia ( 22%). Hypoxia did not affect terbutaline binding affinity to 2-AR. Hypoxia decreased Gs protein levels by 27%, whereas no change was observed in Gi1/2, Gi3, and G subunits. Forskolin-stimulated cAMP production was not inhibited by hypoxia. Pertussis toxin (PTX; 0.5 g/ml, 2 h), an inhibitor of Gi/o proteins, restored terbutaline-stimulated cAMP production of hypoxic ATII cells to normoxic control values. Cholera toxin (CTX)-stimulated Gs protein activity did not change in hypoxia. Hypoxia increased the sensitivity of 2-AR to desensitization. These results indicate that despite the decrease in Gs protein level Gs protein was still functional and that hypoxia impairs 2-AR signaling due to an increased activity of Gi/o proteins.