Alveolar Epithelial Type I Cells Express β2-Adrenergic Receptors and G-protein Receptor Kinase 2

Abstract

β2-Adrenergic agonists stimulate alveolar epithelial sodium (Na+) transport and lung fluid clearance. Alveolar type II (AT2) cells have been reported to express β2-adrenergic receptors (β2AR). Given the large surface area covered by alveolar type I (AT1) cells and their potential role in alveolar fluid removal, we were interested in learning if AT1 cells express β2AR as well. Because β2AR is potentially susceptible to desensitization by G-protein-coupled receptor kinase 2 (GRK2), we also undertook localization of GRK2. β2AR and GRK2 expression was evaluated in whole lung, isolated alveolar epithelial cells (AECs), and AECs in primary culture, and was localized to specific AEC phenotypes by immunofluorescence techniques. β2AR is highly expressed in AT1 cells. β2AR mRNA increases with time in culture as AT2 cells transdifferentiate towards the AT1 cell phenotype. Immunoreactive GRK2 is seen in both AT1 and AT2 cells in similar amounts. These data suggest that both AT1 and AT2 cells may contribute to the increased alveolar Na+ and water clearance observed after exposure to β2 adrenergic agents. Both cell types also express GRK2, suggesting that both may undergo desensitization of β2AR with subsequent decline in the stimulatory effects of β2-adrenergic agonists over time.