Effect of platelet-activating factor on glycogen metabolism in fetal rat lung.
Platelet-activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, or PAF) has previously been shown to induce glycogenolysis in the perfused adult rat liver and in the lung and liver of 24 day (gestational age) fetal rabbits in utero. In the present report, the effect of PAF was examined in fetal rats that were intravenously injected (through the vitellin vein) at a stage in their gestational development characterized by rapid glycogen depletion and surfactant accumulation. At 24 h after PAF administration of 2.5 micrograms and 5.0 micrograms to 19.5- and 20.5-day-old fetal rats, respectively, the lung glycogen content decreased significantly. In contrast, the inactive enantiomer of PAF did not modify the glycogenolytic response in vivo. When [14C]glucose (5 muCi) and PAF (5 micrograms) were simultaneously injected through the vitellin vein of the fetus, the radioactivity incorporated into lung glycogen was reduced as compared with control fetuses receiving the vehicle alone. An additional effect of PAF was noted in experiments designed to correlate glycogen breakdown to surfactant phospholipid biosynthesis. An inhibition of [3H]choline uptake and incorporation into phospholipids of fetal human lung explants and fetal lung type II pneumonocytes was induced by PAF. It is concluded that PAF appears to be a potential inducer of glycogen breakdown in the fetal lung and the relationship of these findings to fetal lung maturation is discussed.
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235.
J R
JR
Bourbon
D R
DR
Hoffman
J M
JM
Johnston
D000818:Animals; D002794:Choline / Q000493:pharmacokinetics; D005333:Fetus / Q000378:metabolism*; D005947:Glucose / Q000493:pharmacokinetics; D006003:Glycogen / Q000378:metabolism*; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D009924:Organ Culture Techniques; D010713:Phosphatidylcholines / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D010713:Phosphatidylcholines; D010972:Platelet Activating Factor; D011663:Pulmonary Surfactants; D006003:Glycogen; D005947:Glucose; D002794:Choline