Secretagogues for lung surfactant increase lung uptake of alveolar phospholipids

This study evaluated the effect of known secretagogues for lung surfactant on the uptake of phospholipid from the aveolar space. Synthetic liposomes containing tracer [choline-methyl-3H]dipalmitoyl phosphatidylcholine (DPPC) were instilled endotracheally in anesthetized rats. Lungs were then isolated and perfused under control conditions or with addition of terbutaline (0.1 mM), ATP (1 mM), or a phorbol ester, tradecanoyl phorbol acetate (TPA, 30 ng/ml). Uptake of liposomes was defined as lavage-resistant accumulation of radioactivity in the lung. Uptake at 2 h was 18.2 +/- 0.93% of instilled radioactivity per minute (mean +/- SE, n = 4) under control conditions and was increased by 56-82% in the presence of each of the agonists (P less than 0.05). At 5 min after addition of terbutaline, uptake was unchanged but secretion of phosphatidylcholine (PC) into the alveolar space was significantly stimulated. Internalized diphosphatidylcholine was degraded to aqueous soluble metabolites and also converted to PC containing an unsaturated fatty acid, and this metabolism was significantly stimulated in the presence of each of the secretagogues. These results indicate that known secretagogues for surfactant increase uptake and metabolism of phospholipid, suggesting linkage of these processes in a physiologically regulated surfactant cycle.