Adrenergic and cholinergic regulation of lung surfactant secretion in the isolated perfused rat lung and in the alveolar type II cell in culture.

Abstract

The purpose of this study is to define the hormonal regulation of pulmonary surfactant secretion in two models, the isolated perfused rat lung and the isolated alveolar type II cell in culture. In the perfused lung, both cholinergic and adrenergic stimulation independently increased labeled disaturated phosphatidylcholine secretion, the major phospholipid component of surfactant, each by 2.3-fold. A concomitant increase in lung cGMP and cAMP concentration of 275- and 25-fold, respectively, was observed. The effect of each agonist was inhibited only by its appropriate antagonist. In alveolar type II cells in culture, both adenylate and guanylate cyclase responded to their appropriate agonists and antagonists. The release of 3H-labeled disaturated phosphatidylcholine was enhanced by beta-adrenergic but not alpha-adrenergic or cholinergic agonists. The effect of isoproterenol (10 microM) on surfactant release was seen by 2.5 min, and secretion was stimulated 2.9-fold at a half-maximal concentration of 1 nM. Cyclic AMP levels were increased by 4.9-fold by isoproterenol at a half-maximal concentration of 40 nM. These results indicate that while in the perfused lung, secretion is stimulated by both adrenergic and cholinergic effectors, in the type II cell model, surfactant secretion is under only beta-adrenergic control.