Effects of β2-adrenergic receptor overexpression on alveolar epithelial active transport

• Published in: Journal of allergy and clinical immunology Vol. 110; no. 6; pp. S242 - S246
• Main Authors: Factor, Phillip, Adir, Yochai, Mutlu, Gökhan M., Burhop, James, Dumasius, Vidas
• Format: Journal Article
• Language: English
• Published: Mosby, Inc 01-12-2002
• Subjects: alveolar epithelium; Alveolar fluid clearance; gene transfer; pulmonary edema; β2-adrenergic receptor; pulmonary edema; adβ2AR; gene transfer; Alveolar fluid clearance; adNull; ATPase; ENaC; cAMP; βAR; alveolar epithelium; GRK2; β2-adrenergic receptor; AFC
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1067/mai.2002.129706

β-Adrenergic receptor (βAR) agonists accelerate the clearance of edema from the alveolar airspace by increasing the function of epithelial transport proteins, including epithelial Na+ channels and Na,K-adenosinetriphosphatases. To improve our understanding of the role of the β2AR in regulating alveolar fluid clearance, we used an adenoviral-mediated gene transfer strategy to effect significant increases in membrane-bound β2AR number and function in the alveolar epithelium of normal rats. Alveolar fluid clearance in β2AR-overexpressing lungs, measured by means of an isolated lung model in the absence of catecholamine supplementation, was 100% greater than in controls. These findings were associated with significant increases of epithelial Na+ channel function and Na,K-adenosine triphosphatase function in the peripheral lung. Experiments performed with adrenalectomized rats, a β2-agonist (procaterol), and a nonspecific β-antagonist (propranolol) indicate that overexpression maximally up-regulates β2-adrenergic-responsive alveolar fluid clearance and improves responsiveness to endogenous catecholamines. Mechanistic studies in human lung epithelial cells (A549) indicate that receptor overexpression prevents homologous receptor desensitization, possibly by overwhelming endogenous regulatory pathways. Our studies demonstrate that overexpression of β2AR in lung epithelial cells can be used to study the role and regulation of alveolar β2ARs. They also suggest a therapeutic role for the β2AR in the treatment of pulmonary edema. (J Allergy Clin Immunol 2002;110:S242-6.)