Effects of Corticosteroids, Prostaglandin E₂, and Beta-Agonists on Adenylate Cyclase Activity in Fetal Rat Lung Fibroblasts and Type II Epithelial Cells

Abstract

The effect of glucocorticoids on the response of adenylate cyclase in fetal rat lung fibroblast and Type II epithelial cell cultures to beta-agonists and prostaglandin E₂ (PGEJ was investigated. There was significant stimulation of cyclic AMP synthesis by adrenalin in both fibroblasts and Type II cells, which was potentiated in a dose-dependent manner by Cortisol. Stimulation of adenylate cyclase by PGE₂ (10-1000 nM) was demonstrated in fibroblasts but not in Type II cells. The response to PGE₂ was stimulated by pretreatment with Cortisol only in fibroblasts (p < .01), and no latent response to PGE₂ was evident in Type II cells after Cortisol treatment. These experiments suggest that both cell types isolated from late gestation fetal lung contain active beta-agonist and glucocorticoid receptors that synergize in raising intracellular cyclic AMP, which has multiple effects, including surfactant secretion from Type II cells. Since the adenylate cyclase response to PGE₂ and its enhancement by glucocorticoids occurred only in fibroblasts, it is concluded that the reported effects ofPGE₂ on surfactant release are not mediated via raised intracellular cyclic AMP in Type II cells.