Cytidine monophosphate-dependent synthesis of phosphatidylglycerol in permeabilized type II pneumonocytes.
Results of previous investigations support the proposition that, in type II pneumonocytes, CMP is involved in integration of the synthesis of phosphatidylcholine and phosphatidylglycerol for lung surfactant. In the present investigation, the amount of CMP in rat type II pneumonocytes was altered directly and resultant changes in the synthesis of phosphatidylglycerol were examined. Type II pneumonocytes were made permeable to CMP by treatment with Ca2+-free medium, and phosphatidylglycerol synthesis was then assessed by measurement of the incorporation of a radiolabelled precursor, [14C]glycerol 3-phosphate, that was not effectively utilized by cells that resisted permeabilization. Incorporation of [14C]glycerol 3-phosphate into phosphatidylglycerol (but not into other lipids) was stimulated greatly by CMP (half-maximal stimulation at approx. 0.1 mM). CMP stimulated the incorporation of [14C]glycerol 3-phosphate into both the phosphatidyl moiety and the head group of phosphatidylglycerol. Incorporation of [14C]palmitate into phosphatidylglycerol was also stimulated by CMP. myo-Inositol, at concentrations found in foetal-rat serum (0.2-2.0 mM), inhibited CMP-dependent incorporation of [14C]glycerol 3-phosphate into phosphatidylglycerol and promoted, instead, CMP-dependent incorporation into phosphatidylinositol. These data, when extrapolated to foetal type II pneumonocytes, are consistent with the view that the developmental increase in the synthesis of phosphatidylglycerol for surfactant by foetal lungs is promoted by the increase in intracellular CMP and the declining availability of myo-inositol that were found previously to be associated with this period of development.
D000249:Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D003568:Cytidine Monophosphate / Q000494:pharmacology*; D003597:Cytosine Nucleotides / Q000494:pharmacology*; D005994:Glycerophosphates / Q000378:metabolism; D006157:Guanosine Monophosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D007294:Inositol / Q000494:pharmacology; D050356:Lipid Metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology; D010715:Phosphatidylglycerols / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D003597:Cytosine Nucleotides; D005994:Glycerophosphates; D010169:Palmitic Acids; D010715:Phosphatidylglycerols; D019308:Palmitic Acid; D000249:Adenosine Monophosphate; D007294:Inositol; D006157:Guanosine Monophosphate; C029620:alpha-glycerophosphoric acid; D003568:Cytidine Monophosphate