期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 296, 期 3, 页码 L500-L509出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.90390.2008
关键词
lung; adenosine 3 ',5 '-cyclic adenosine monophosphate; G proteins; pulmonary edema
资金
- German Research Foundation (DFG) [Ma 1503/18-2]
Baloglu E, Ke A, Abu-Taha IH, Ba r rtsch P, Mairbaurl H. In vitro hypoxia impairs beta(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 beta(2)-adrenergic receptor (beta(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 beta(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% O-2) 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 beta(2)-AR assessed by (-)-[I-125] iodocyanopindolol binding was decreased in hypoxia (-22%). Hypoxia did not affect terbutaline binding affinity to beta(2)-AR. Hypoxia decreased G(s) protein levels by 27%, whereas no change was observed in G(i1/2), G(i3), and G beta subunits. Forskolin-stimulated cAMP production was not inhibited by hypoxia. Pertussis toxin (PTX; 0.5 mu g/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 beta(2)-AR to desensitization. These results indicate that despite the decrease in G(s) protein level Gs protein was still functional and that hypoxia impairs beta(2)-AR signaling due to an increased activity of G(i/o) proteins.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据