Effects of cyclic AMP analogues and phosphodiesterase inhibitors on phospholipid biosynthesis in fetal type II pneumocytes.
Purified type II pneumocytes grown in monolayer cultures after isolation from fetal rabbit lung organotypic cultures were employed to investigate effects of cAMP analogues and phosphodiesterase inhibitors on [methyl-14C]choline and [9-10(n)3H]palmitate incorporation into cell lipids. After 24 h exposure to 0.5 mM N6,O2-dibutyryl-cAMP or 8-bromo-cAMP, a significant increase was found in the rate of incorporation of choline into phospholipids. Addition of 1 mM 1-methyl-3-isobutylxanthine or aminophylline also increased incorporation of choline into phospholipids but did not significantly change the incorporation of choline into sphingomyelin. These effects were not due to increased uptake of choline or changes in the pool size of the precursor. Cyclic AMP analogues also stimulated the rate of incorporation of palmitate into most lipid fractions but did not alter the relative percentages of incorporation of either precursor into any of the phospholipids. Phosphodiesterase inhibitors did not significantly change the rate of incorporation of palmitate into neutral lipids and most phospholipids, except for a decrease into sphingomyelin, phosphatidylinositol and phosphatidylethanolamine. However, they increased the percentage of incorporation of palmitate into phosphatidylcholine and decreased the percentage of incorporation into most other phospholipids. These data clearly indicate that cAMP can stimulate the synthesis of phospholipids within the type II pneumocytes. This effect is probably a general stimulation effect for the cAMP analogues but methylxanthines may selectively increase the synthesis of surfactant lipids such as phosphatidylcholine while decreasing that of other membrane-associated phospholipids.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology*; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000096:biosynthesis*; D011817:Rabbits
D010169:Palmitic Acids; D010726:Phosphodiesterase Inhibitors; D011663:Pulmonary Surfactants; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000628:Aminophylline; D019308:Palmitic Acid; D000242:Cyclic AMP; D002794:Choline