Perinatal Development of Myoinositol Uptake into Lung Cells: Surfactant Phosphatidylglycerol and Phosphatidylinositol Synthesis in the Rabbit

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Abstract
It has been proposed that the high serummyoinositol promotes fetal growth and affects developmentof lung surfactant. However, it is unclear how the extra-cellular myoinositol becomes available in specific cells andwhether there are developmental differences in myoinositoluptake. In the present study the mechanisms and perinataldevelopment of intracellular myoinositol uptake into rabbitlung cells were investigated. Lung slices, lung explants,and type II alveolar cells were used. Evidence of saturable,sodium- and energy-dependent, and of non-saturable, so-dium- and energy-independent myoinositol uptake wasfound. The nonsaturable uptake decreased by 67% duringspontaneous maturation, as studied in lung slices. Beta-methasone (0.2 nig/kg days 26.3 and 27.3, to the doe)decreased by 65% the nonsaturable myoinositol uptake in28-day-old fetuses. However, the saturable uptake revealedonly small changes during perinatal development. Theeffect of extracellular myoinositol on surfactant phospho-lipid synthesis was evaluated in lung explants from 28-day-old fetuses, cultured for 2 days. In the presence of 10−6 dexamethasone the concentration of extracellularmyoinositol, required for half-maximal inhibition of sur-factant phosphatidylglycerol incorporation was higher thanin explants grown without the hormone (approximately 0.4versus 0.2 mM). However, in the microsomal fraction thephosphatidylglycerol incorporation was always inhibitedby as low as 4 nM myoinositol. Myoinositol was taken upby isolated type II cells preferably by nonsaturable mech-anism. The phosphatidylglycerol incorporation was lesssensitive to extracellular myoinositol in adult than in fetalcells. Although there were only small changes in the con-centration of free myoinositol in whole lung during peri-natal development, the availability of this sugar alcohol tosome specific cells decreased strikingly due to a decreasein serum concentration and a decrease in permeability ofthis putative growth factor. The present findings demon-strate that some cells within myoinositol-rich tissue can bedevoid of this sugar alcohol and critically depend on extra-cellular source for their myoinositol supply.