Submitted on July 22, 2008
Revised on December 1, 2008
Accepted on December 17, 2008
In vitro hypoxia impairs beta 2 adrenergic receptor signaling in primary rat alveolar epithelial cells
Emel Baloglu1, Alberto Ke1, Issam Hissam Abu-Taha2, Peter Bartsch1, and Heimo Mairbaurl1*
1 University of Heidelberg
2 University of Heidelberg/Mannheim
* To whom correspondence should be addressed. E-mail: heimo.mairbaeurl{at}med.uni-heidelberg.de.
Hypoxia inhibits 
2AR-signaling in a variety of tissues, but effects in alveolar epithelium are unclear. We therefore examined the effect of 24 hour of hypoxia on 2AR function in primary rat alveolar epithelial (AII) cells. AII cells were isolated, cultured to confluence, and incubated in normoxia or hypoxia (3% O2) for 24 hours. Hypoxia decreased maximal terbutaline-stimulated cAMP production by 37%; potency of terbutaline was not affected. Reoxygenation (3h) reversed this effect. Density of 2AR assessed by ICYP binding was decreased in hypoxia (-22%). Hypoxia did not affect terbutaline binding affinity to 2AR. 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 µg/ml, 2 hour), an inhibitor of Gi/o proteins, restored terbutaline-stimulated cAMP production of hypoxic AII cells to normoxic control values. Cholera toxin (CTX)-stimulated Gs protein activity did not change in hypoxia. Hypoxia increased the sensitivity of 2AR to desensitization. These results indicate that despite the decrease in Gs protein level, Gs protein was still functional and that hypoxia impairs 2AR signaling due to an increased activity of Gi/o proteins.
