myo-Inositol homeostasis in foetal rabbit lung

Abstract

In several species, lung maturation is accompanied by a decline in the phosphatidylinositol content of lung surfactant and a concomitant increase in its phosphatidylglycerol content. To examine the possibility that this developmental change is influenced by the availability of myo-inositol, potential sources of myo-inositol for the developing rabbit lung were investigated. On day 28 of gestation the myo-inositol content of foetal rabbit lung tissue (2.3+/-0.5mumol/g of tissue) was not significantly different from that of adult lung tissue but the activity of d-glucose 6-phosphate:1l-myo-inositol 1-phosphate cyclase (cyclase) in foetal lung tissue (81.0+/-9.0nmol.h(-1).g of tissue(-1)) was higher than that found in adult lung tissue (23.2+/-1.0nmol.h(-1).g of tissue(-1)). Day 28 foetal rabbit lung tissue was found also to take up myo-inositol by a specific, energy-dependent, Na(+)-requiring mechanism. Half-maximal uptake of myo-inositol by foetal rabbit lung slices was observed when the concentration of myo-inositol in the incubation medium was 85mum. When the myo-inositol concentration was 1mm (but not 100mum) the addition of glucose (5.5mm) stimulated myo-inositol uptake. myo-Inositol uptake was observed also in adult rabbit lung and was found to be sub-maximal at the concentration of myo-inositol found in adult rabbit serum. The concentration of myo-inositol in the serum of pregnant adult rabbits (47.5+/-5.5mum) was significantly lower than that of non-pregnant adult female rabbits (77.9+/-9.2mum). On day 28 of gestation the concentration of myo-inositol in foetal serum (175.1+/-12.0mum) was much less than on day 25, but more than that found on day 30. A transient post-partum increase in the concentration of myo-inositol in serum was followed by a rapid decline. Much of the myo-inositol in foetal rabbit serum probably originates from the placenta, where on day 28 of gestation a high cyclase activity (527+/-64nmol.h(-1).g of tissue(-1)) was measured. The gestational decline in serum myo-inositol concentration, together with the decreasing cyclase activity of the lungs, is consistent with the view that maturation of the lungs is accompanied by decreased availability of myo-inositol to this tissue.

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

“…In the present day 21 is consistent with previous observations in investigation, however, the acidic extraction conthe rabbit [3] and in man [21] and is compatible ditions that were employed resulted in the hydrowith the proposition that late in gestation there is lysis of ethanolamine plasmalogen and so it would a decreasing availability of myo-inositol for PI not have contributed to the measured amounts of biosynthesis in fetal rat lung, myo-inositol avail-phosphatidylethanolamine [16]. ability to the fetal lung may therefore be an The presence of myo-inositol in increased concenimportant regulator of the developmental change trations in maternal and fetal rat serum resulted in from the production of a surfactant rich in PI to a significantly reduced PG/PI ratio in lung tissue one rich in PG.…”

“…The lungs were then dissected from the thorax and kept at 4°C until processed further. myo-inositol was measured in adult and fetal blood by gas-liquid chromatography of its trimethylsilyl (TMS) derivative as described previously [3]. The amount of TMS-myo-inositol in each extract was computed by measurement of peak area relative to the peak areas obtained with The values (Mean ± SE) for adult rats represent all measurements obtained on days 1,3, and 5 of treatment.…”

“…The group of rats injected with myoinositol also had drinking water containing myoinositol (7% w/v.). Blood samples were obtained from the tail vein of the rats and processed for measurement of myo-inositol [3]. In experiments utilizing pregnant rats, the animals were sacrificed on day 18 or day 21 of gestation with a lethal dose of Nembutal.…”

“…During lung development in the human and in other species, the PG content of surfactant rises with a concomitant fall in phosphatidylinositol (PI) content. It has been proposed that the relative rates of synthesis of PI and PG for surfactant may be influenced by the availability of myo-inositol in the lung [3,15]. In many tissues, the limited amount of CDP-diacylglycerol that is present likely restricts the biosynthesis of both PI and PG and it has been observed in vitro that the metabolic fate of CDPdiacylglycerol is influenced by the extracellular concentration of myo-inositol [8,10,11].…”

“…It .has been observed also that excess myo-inositol administered to adult rabbits decreased surfactant PG and increased surfactant PI [14]. We have examined previously myo-inositol homeostasis in the fetal rabbit [3] and in the human fetus [21], Based on the results of those studies we concluded that lung development in the human and in the rabbit is accompanied by decreased availability of myo-inositol for surfactant PI biosynthesis. In addition, we observed that myo-inositol (in concentrations similar to those measured in vivo) affected the incorporation of { 14 C} glycerol into glycerophospholipids by fetal rabbit lung explants [18] and by type II pneumonocytes isolated from adult rat lung [4].…”