Adenosine and leukotrienes have a regulatory role in lung surfactant secretion in the newborn rabbit

Previous studies have shown that secretion of phosphatidylcholine in cultured adult rat type II pneumocytes is stimulated by purinoceptor agonists and leukotrienes. The objective of the present study was to determine if such agents have a physiological role in the regulation of surfactant secretion. We chose the newborn rabbit as the experimental model, since in this system there is a marked increase in surfactant secretion immediately after birth. We examined the effects of an inhibitor of leukotriene biosynthesis, nordihydroguaiaretic acid, two leukotriene antagonists, FPL-55712 and FPL-57231, and a P1 purinoceptor antagonist, 8-phenyltheophylline, on this increase. Newborn rabbits were delivered by Cesarean section at 30 days gestation. Some animals in each litter were killed immediately, while others were injected with test agents or solvent vehicle while still in the amniotic sacs. After breathing for 3 h in an incubator, these animals were also killed. The lungs were lavaged with saline and the phospholipid content and composition of the lung lavage liquid was measured. In control animals, there was a greater than 2-fold increase in the amounts of total phospholipid and phosphatidylcholine and in the phosphatidylcholine/sphingomyelin ratio during the 3 h period of breathing. The increases in total phospholipid and phosphatidylcholine were decreased 38-62% by the antagonists, while the increase in the phosphatidylcholine/sphingomyelin ratio was decreased 61-77%. These data show that the ventilation-induced increase in secretion of lung surfactant in the newborn rabbit is inhibited by leukotriene and P1 receptor antagonists and by an inhibitor of leukotriene biosynthesis and, when taken together with the data from the tissue culture system, support a role for leukotrienes and adenosine in the physiological regulation of surfactant secretion.