Aminophylline stimulates the incorporation of choline into phospholipid in explants of fetal rat lung in organ culture

Abstract

We have investigated the direct effect of aminophylline, a cyclic AMP phosphodiesterase inhibitor, and of cyclic AMP on choline incorporation into phospholipid in explants of fetal rat lung in organ culture. Explants from 19 day fetal rat lung (term is 22 days) were cultured for 24 or 48 h in F12 medium containing 1.0 mM aminophylline or 0.2 mM dibutyryl cyclic AMP. Explants cultured in F12 medium alone served as controls. Exposure to aminophylline resulted in an 88% increase in choline incorporation into phosphatidylcholine ( P < 0.01) and a 95% increase in choline incorporation into sphingomyelin ( P < 0.001) in the 48-h cultures. Similar changes were noted after 24 h in culture. There was a small increase in the percentage of synthesized phosphatidylcholine which was disaturated. The activities of choline kinase and cholinephosphotransferase in the explants were not significantly altered by exposure to aminophylline. 77 and 53% stimulation of choline incorporation into phosphatidylcholine and sphingomyelin respectively was demonstrated in explants cultured in medium containing cyclic AMP. Aminophylline treatment of explants from 20- and 21-day fetuses resulted in a smaller degree of stimulation of choline incorporation into both phospholipids. These data suggest that aminophylline has a direct stimulatory effect on the incorporation of choline into phospholipid in fetal rat lung and that this effect is probably cyclic AMP mediated.