title: Alveolar epithelial type I cells express beta2-adrenergic receptors and G-protein receptor kinase 2.
abstract: Beta2-Adrenergic agonists stimulate alveolar epithelial sodium (Na(+)) transport and lung fluid clearance. Alveolar type II (AT2) cells have been reported to express beta2-adrenergic receptors (beta2AR). 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 beta2AR as well. Because beta2AR is potentially susceptible to desensitization by G-protein-coupled receptor kinase 2 (GRK2), we also undertook localization of GRK2. beta2AR 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. beta2AR is highly expressed in AT1 cells. beta2AR 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 beta2 adrenergic agents. Both cell types also express GRK2, suggesting that both may undergo desensitization of beta2AR with subsequent decline in the stimulatory effects of beta2-adrenergic agonists over time.
authors.affiliation: Will Rogers Institute Pulmonary Research Center, Division of Pulmonary and Critical Care Medicine, University of Southern California, Los Angeles, California 90033, USA. liebler@usc.edu
authors.forename: Janice M
authors.initials: JM
authors.lastname: Liebler
authors.forename: Zea
authors.initials: Z
authors.lastname: Borok
authors.forename: Xian
authors.initials: X
authors.lastname: Li
authors.forename: Beiyun
authors.initials: B
authors.lastname: Zhou
authors.forename: Argelia J
authors.initials: AJ
authors.lastname: Sandoval
authors.forename: Kwang-Jin
authors.initials: KJ
authors.lastname: Kim
authors.forename: Edward D
authors.initials: ED
authors.lastname: Crandall
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D054769:G-Protein-Coupled Receptor Kinase 2; D008297:Male; D010641:Phenotype; D011650:Pulmonary Alveoli / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis*; D051552:beta-Adrenergic Receptor Kinases
chemical_list: D018343:Receptors, Adrenergic, beta-2; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; C496569:Grk2 protein, rat; D051552:beta-Adrenergic Receptor Kinases; D054769:G-Protein-Coupled Receptor Kinase 2