HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 296/3/L500    most recent 90390.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Baloglu, E. Articles by Mairbäurl, H. Search for Related Content PubMed PubMed Citation Articles by Baloglu, E. Articles by Mairbäurl, H.

In vitro hypoxia impairs β₂-adrenergic receptor signaling in primary rat alveolar epithelial cells

Emel Balolu,¹ Alberto Ke,¹ Issam Hissam Abu-Taha,² Peter Bärtsch,¹ and Heimo Mairbäurl¹

¹Medical Clinic VII, Sports Medicine, University Hospital Heidelberg, University of Heidelberg, Heidelberg; and ²Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

Submitted 22 July 2008 ; accepted in final form 17 December 2008

Hypoxia inhibits β₂-adrenergic receptor (β₂-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 β₂-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 β₂-AR assessed by (–)-[¹²⁵I]iodocyanopindolol binding was decreased in hypoxia (–22%). Hypoxia did not affect terbutaline binding affinity to β₂-AR. Hypoxia decreased G_s protein levels by 27%, whereas no change was observed in G_i1/2, G_i3, and Gβ subunits. Forskolin-stimulated cAMP production was not inhibited by hypoxia. Pertussis toxin (PTX; 0.5 µg/ml, 2 h), an inhibitor of G_i/o proteins, restored terbutaline-stimulated cAMP production of hypoxic ATII cells to normoxic control values. Cholera toxin (CTX)-stimulated G_s protein activity did not change in hypoxia. Hypoxia increased the sensitivity of β₂-AR to desensitization. These results indicate that despite the decrease in G_s protein level G_s protein was still functional and that hypoxia impairs β₂-AR signaling due to an increased activity of G_i/o proteins.

lung; adenosine 3',5'-cyclic adenosine monophosphate; G proteins; pulmonary edema