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In many species including man, the second most abundant lipid in lung surfactant is phosphatidylglycerol (PG) which may comprise 10% of the total lipid in surfactant from mature lungs. Infants delivered before their surfactant contained a large amount of PG are at greater risk of succumbing to hyaline membrane disease. Regulation of the PG content of lung surfactant is not understood completely, but the reciprocal changes in the amount of phosphatidylinositol (PI) and PG in surfactant as the lung mature are suggestive of regulation at the level of a common precursor. The immediate common precursor of PI and PG is CDP-diacylglycerol which is found in only small amounts in most mammalian cells and likely restricts the biosynthesis of both PI and PG. It has been observed in several species that the enzymes that synthesize PI and PG compete for the limited amount of CPD-diacylglycerol and this competition is influenced by the availability of myo-inositol. We and others have presented evidence that myo-inositol availability in the developing lung may be an important factor in the regulation of lung surfactant composition. In the present investigation, myo-inositol was administered chronically to nonpregnant and to pregnant rats and the effect of this treatment on the glycerophospholipid composition of lung tissue and lung lavage was measured. In addition, the influence of myo-inositol administration to pregnant rats on the glycerophospholipid composition of lung tissue of their fetuses was investigated. The concentration of myo-inositol in adult and fetal blood was measured by gas-liquid chromatography of its trimethylsilyl derivative. For determination of glycerophospholipid composition, the total lipid extracts of lung tissues and lung lavage were separated by 2-dimensional thin-layer chromatography and quantified by lipid phosphorus assay of individual spots. The concentration of myo-inositol in the serum of pregnant rats was significantly higher than in nonpregnant rats (Tab. I, Fig. 1). Treatment of the rats with myo-inositol resulted in a significant elevation of serum concentrations of myo-inositol throughout the experimental period. Between day 18 and day 21 of the gestation there was a significant decrease in serum myo-inositol concentrations in fetuses of saline treated rats. Treatment of the pregnant dams with myo-inositol resulted in a significant elevation in fetal serum concentrations of myo-inositol on both day 18 and day 21 of gestation (Tab. I).(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of myo-inositol on the glycerophospholipid composition of adult and fetal rat lung tissue