Alveolar epithelial beta2-adrenergic receptors

Abstract

beta(2)-adrenergic receptors are present throughout the lung, including the alveolar airspace, where they play an important role for regulation of the active Na(+) transport needed for clearance of excess fluid out of alveolar airspace. beta(2)-adrenergic receptor signaling is required for up-regulation of alveolar epithelial active ion transport in the setting of excess alveolar edema. The positive, protective effects of beta(2)-adrenergic receptor signaling on alveolar active Na(+) transport in normal and injured lungs provide substantial support for the use of beta-adrenergic agonists to accelerate alveolar fluid clearance in patients with cardiogenic and noncardiogenic pulmonary edema. In this review, we summarize the role of beta(2)-adrenergic receptors in the alveolar epithelium with emphasis on their role in the regulation of alveolar active Na(+) transport in normal and injured lungs.

Figure 1.

Effects of β₂-adrenergic receptor activation in alveolar epithelial cells. Activation of β₂-adrenergic receptor (β₂AR) increases alveolar active Na⁺ transport via upregulation of epithelial Na⁺ channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR) as well as basolaterally located Na,K-ATPase (open arrows). Activation of the receptor also increases β-catenin and surfactant release, which might be important in the pathogenesis/resolution of acute lung injury. ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; PKA, protein kinase A.

Figure 2.

Proposed interaction of β₂-adrenergic receptor with CFTR and other proteins. In the cell membrane, the β₂AR is in close proximity to transport molecules such as CFTR and possibly ENaC. This macromolecular complex is maintained through interactions of the β₂AR with scaffold and adaptor proteins including EBP50 and ezrin, which also link the receptor with submembrane cytoskeletal elements. ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; EBP50, ezrin-radixin-moesin-binding phosphoprotein 50; PKA, protein kinase A. (Adapted from Reference .)