Delayed pulmonary phosphatidylglycerol synthesis and reversal by prenatal dexamethasone in fetal rats of streptozotocin-diabetic mothers

Lung slices from fetal rats of streptozotocin-diabetic mothers incorporated [3H]glycerol and [3H]choline into phosphatidylglycerol and disaturated phosphatidylcholine, respectively. When compared to age-matched fetuses from nondiabetic mothers, lung phosphatidylglycerol synthesis of 21-day fetuses of diabetic mothers was significantly diminished, although [3H]glycerol incorporation into other phospholipids was not impaired. Synthesis of disaturated phosphatidylcholine was not diminished in lungs of 20-, 21-, or 22-day fetuses of diabetic mothers. Prenatal dexamethasone partially reversed the diminished phosphatidylglycerol synthesis at 21 days of gestation; the degree of stimulation was the same as that seen in 21-day fetuses of normal mothers but the maximal rate of [3H]glycerol incorporation was about 60% of that in 21-day fetuses of normal mothers. Fetal lung disaturated phosphatidylcholine synthesis was not stimulated by dexamethasone in diabetic pregnancies, in contrast to that seen in nondiabetic pregnancies. These data suggest that maternal diabetes interferes with the ability of fetal lungs to synthesize phosphatidylglycerol, a finding consistent with the delayed appearance of phosphatidylglycerol in the amniotic fluid of human diabetic pregnancies. In addition, maternal diabetes impairs the responsiveness of disaturated phosphatidylcholine synthesis to dexamethasone. Since phosphatidylglycerol synthesis is enhanced by prenatal dexamethasone, this therapy may still be effective for reducing the adverse impact of maternal diabetes on fetal lung development.     

Neurohumoral control of pulmonary surfactant secretion

The effect of the muscarinic drug, carbamylcholine, on surfactant secretion by hamster lung was examined. Intracellular phosphatidylcholine was prelabeled with tritium by intraperitoneal injection of [³H]choline into adult hamsters. Carbamylcholine (18 µg/100 g body wt.) was administered IP to one group of animals 30 min before sacrifice and isotonic saline was given to another group. Following sacrifice, the lungs were perfused, sliced, and incubated in the presence or absence of 15 µg/ml carbamylcholine for 1 h. Secretion of radiolabeled phosphatidylcholine by the lung tissue slices into the medium was evaluated. Treatment of animals with carbamylcholine was associated with a significant enhancement in the secretion of [³H]phosphatidylcholine into the medium. Administration of the muscarinic antagonist, atropine, in an equimolar dose completely inhibied the stimulatory effect of carbamylcholine on surfactant secretion. Treatment of hamster fetuses with carbamylcholine had no effect on [³H]phosphatidylcholine secretion from fetal lung tissue slices. The results support the concept that surfactant secretion by adult hamster lung is regulated by neurohumoral mechanisms.     

Neurohumoral control of pulmonary surfactant secretion

The effect of the muscarinic drug, carbamylcholine, on surfactant secretion by hamster lung was examined. Intracellular phosphatidylcholine was prelabeled with tritium by intraperitoneal injection of [³H]choline into adult hamsters. Carbamylcholine (18 µg/100 g body wt.) was administered IP to one group of animals 30 min before sacrifice and isotonic saline was given to another group. Following sacrifice, the lungs were perfused, sliced, and incubated in the presence or absence of 15 µg/ml carbamylcholine for 1 h. Secretion of radiolabeled phosphatidylcholine by the lung tissue slices into the medium was evaluated. Treatment of animals with carbamylcholine was associated with a significant enhancement in the secretion of [³H]phosphatidylcholine into the medium. Administration of the muscarinic antagonist, atropine, in an equimolar dose completely inhibied the stimulatory effect of carbamylcholine on surfactant secretion. Treatment of hamster fetuses with carbamylcholine had no effect on [³H]phosphatidylcholine secretion from fetal lung tissue slices. The results support the concept that surfactant secretion by adult hamster lung is regulated by neurohumoral mechanisms.     

Biochemical and metabolic properties of bovine type II pneumocytes in primary culture

Bovine type II pneumocytes were isolated from lungs of adult cattle by enzymatic tissue dissociation and subsequent purification by density gradient centrifugation on a 1.040 g/ml Percoll gradient. By quantitative and qualitative high-performance liquid chromatographic (HPLC) analysis of freshly isolated, highly purified bovine type II pneumocytes, six phospholipid components (phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, and sphingomyelin) were detected regularly and their composition was compared to that of whole lung homogenates. Total phospholipid content of 10⁶ bovine type II cells was 34.7 μg (quantitative HPLC). Suspended and adherent bovine type II cells incorporated [¹⁴C]choline into their phospholipids. The rate of synthesis of suspended cells (289 pmol/h×10⁶ cells) was constant for at least 4 h, while adherent type II cells incorporated [¹⁴C]choline with a constant rate of 160 pmol/h×10⁶ cells for at least 20 h. These data further establish the use of cultured bovine type II pneumocytes as a high-purity model for the in vitro investigation of the surfactant system.     

Turnover and recycling of glucose in man during prolonged fasting

The effect of prolonged (3–5 wk) fasting on tracer-determined glucose turnover and of recycling radioactive glucose has been examined. We followed the specific activity of plasma glucose after the simultaneous administration of 1-¹⁴C-glucose and 3-³H-glucose. The rate of glucose turnover decreased during prolonged fasting. Recycling of radioactive glucose was estimated by two different techniques: (1) the appearance of ¹⁴C in positions 2 to 6 glucose was measured; (2) the difference in the slopes of specific activity decline for 1-¹⁴C-glucose and for 3-³H-glucose was calculated. The two methods of estimating the radioactive recycling gave results similar to each other. The amount of glucose recycled did not change during prolonged fasting. However, in view of the decline in glucose production during fasting, the proportion of glucose production which was represented by recycling increased. Based on weight and urinary nitrogen loss an estimate of the glucose production from amino acids and glycerol was obtained. The difference between the rate of glucose production from the contribution of amino acids and glycerol and that estimated by radioisotopic techniques was much larger than the measured rate of recycling. This finding suggests that either a large exchange of ¹²C with ¹⁴C occurred in some glycolytic intermediates or that a hitherto unknown source of carbon for glucose production appeared during prolonged fasting.     

The perfused isolated lung as a possible model for the study of lipid synthesis by type II cells in their natural environment

The incorporation of radioactively labeled palmitate and acetate into total and disaturated phosphatidylcholines was studied in the perfused whole lung, in surfactant secreted during perfusion, and in isolated alveolar type II cells. Exogenously added palmitate was found to be incorporated preferentially into the 2-position of total and disaturated phosphatidylcholines in all cases. Acetate, when supplied at a high concentration, was incorporated preferentially into the 2-position in all cases. However, acetate supplied at a low concentration was incorporated preferentially into the 2-position in type II cells and in surfactant, but preferentially into the 1-position in the whole lung. The dissimilarity in incorporation of acetate between isolated type II cells and perfused whole lung and the similarity in this respect between isolated type II cells and surfactant indicate that the perfused isolated lung may only be a good model for studying the synthesis of surfactant components by the type II cells in their natural environment if the products of processes in type II cells are separated from products of other cells after the perfusion. Both in surfactant and in lavaged lung tissue, labeled palmitate and acetate incorporated mainly into the 2-position of phosphatidylglycerol. This indicates that remodeling reactions are involved in the synthesis of dipalmitoylphosphatidylglycerol.     

Effect of lactate on glucose incorporation into fetal lung phospholipids

Fetal rabbit lung explants were incubated with 3.0 mM glucose and varying levels of lactate. An increase in lactate concentrations resulted in a decrease in glucose incorporation into total disaturated phosphatidylcholine. Glucose utilization for surfactant phosphatidylcholine synthesis was also reduced by approximately 35% in the presence of 5.0 mM lactate. The decreased incorporation of glucose occurred in the fatty acid portion of both total tissue disaturated phosphatidylcholine and surfactant phosphatidylcholine. The effect of lactate on glucose incorporation into pulmonary phospholipids was not affected by the presence of pyruvate in concentrations up to 500 microM. Pyruvate alone produced only a slight decrease in glucose utilization for lung phospholipid production. These data indicate that glucose and lactate are competitive substrates for late gestation surfactant phospholipid fatty acid synthesis, and that lactate is potentially a very important substrate for fetal lung development.     

Properties of an acid phosphatase in pulmonary surfactant.

Lung surfactant, a lipid-protein complex purified from dog lungs, contains a highly active phosphomonoesterase associated with it. This phosphatase is quite specific for the hydrolysis of phosphatidic acid and 1-acyl-2-lysophosphatidic acid. The enzyme possesses many of the characteristics of the microsomal enzyme, phosphatidate phosphohydrolase (EC 3.1.3.4). In addition, we have shown that this enzyme will also convert phosphatidylglycerol phosphate [1-(3-sn-phosphatidyl)-sn-glycerol-1-P] to phosphatidylglycerol [1-(3-sn-phosphatidyl)-sn-glycerol] and Pi. The phosphatidylglycerol phosphate was made available to the surfactant enzyme in a coupled assay by hydrolysis of cardiolipin [1-(3-sn-phosphatidyl)-3-(3-sn-phosphatidyl)-sn-glycerol] by stereospecific cleavage with phospholipase C (phosphatidylcholine cholinephosphohydrolase, EC 3.1.4.3) from Bacillus cereus. This enzyme has been previously shown to generate the naturally occurring isomer of phosphatidylglycerol phosphate because it has specificity for the 3-(3-sn-phosphatidyl) group of cardiolipin. Other properties of the surfactant enzyme are discussed in relation to its presence in lung surface active material.     

In vitro corticosteroidogenesis by the adrenal gland of the chicken (Gallus domesticus)

[4-¹⁴C]Pregnenolone, [4-¹⁴C]progesterone, and [4-¹⁴C]11-deoxycorticosterone were indubated with chicken adrenal tissue slices, whole homogenates, and subcellular fractions, with and without the addition of ACTH to the incubation medium. Progesterone, 11-deoxycorticosterone, corticosterone, 11β-hydroxyprogesterone, and aldosterone were identified as metabolites of these radioactive precursors. The rate of conversion of pregnenolone to progesterone by the slices and progesterone to corticosterone by the mitochondrial fraction significantly increased by the addition of ACTH to the medium. The activity of Δ⁵-3β-hydroxysteroid dehydrogenase associated with Δ⁵-Δ⁴ isomerase upon pregnenolone and the activity of 21-hydroxylase upon progesterone were concentrated in the microsomal fraction, while the activity of 11β-hydroxylase upon 11-deoxycorticosterone was in the mitochondrial fraction. No 17α-hydroxylase activity was observed.The main pathway for steroidogenesis in the chicken adrenal gland is proposed to be: pregnenolone → progesterone → 11-deoxycorticosterone → corticosterone.     

Biochemical and metabolic properties of bovine type II pneumocytes in primary culture

Bovine type II pneumocytes were isolated from lungs of adult cattle by enzymatic tissue dissociation and subsequent purification by density gradient centrifugation on a 1.040 g/ml Percoll gradient. By quantitative and qualitative high-performance liquid chromatographic (HPLC) analysis of freshly isolated, highly purified bovine type II pneumocytes, six phospholipid components (phosphatidylcholine, phosphatidylglycerol, phosphatidyl-ethanolamine, phosphatidylinositol, phosphatidylserine, and sphingomyelin) were detected regularly and their composition was compared to that of whole lung homogenates. Total phospholipid content of 10(6) bovine type II cells was 34.7 micrograms (quantitative HPLC). Suspended and adherent bovine type II cells incorporated [14C]choline into their phospholipids. The rate of synthesis of suspended cells (289 pmol/h x 10(6) cells) was constant for at least 4 h, while adherent type II cells incorporated [14C]choline with a constant rate of 160 pmol/h x 10(6) cells for at least 20 h. These data further establish the use of cultured bovine type II pneumocytes as a high-purity model for the in vitro investigation of the surfactant system.     

Absence of a nuclear androgen receptor in isolated germinal cells of rat testis

Androgen receptors are known to be present in the seminiferous tubules of rat testis and in the present study it has been attempted to compare the binding of [³H] testosterone to androgen receptors in male germinal cells and Sertoli cells. Cell preparations enriched in germinal cells and Sertoli cells were isolated from testicular tissue of 30–35-day-old rats. The cell preparations were either obtained from intact rats and labelled in vitro with [³H] testosterone or were obtained from the testes of hypophysectomized rats which were labelled in vivo with [³H]testosterone prior to the isolation of the cells. The nuclear fractions of the labelled cell preparations were extracted with 0.4 M KCl and the extracts were fractionated by sucrose density gradient centrifugation to estimate specific binding of radioactive steroid.Specific binding of radioactive steroid to nuclear androgen receptors was observed in Sertoli cell preparations but not in preparations of germinal cells (spermatocytes and round spermatids).     

Developmental changes in phosphatidylinositol transfer protein concentration and phospholipid transfer activities in rat type II cells

The phospholipid transfer proteins (PLTPs) are cytosolic proteins that have been characterized by their ability to facilitate the transfer of phospholipids between membranes in vitro. The goals of this study were to determine whether PITP alpha concentration and phospholipid transfer activities are enriched in type II cells compared with whole lung and to determine the developmental changes in PITP alpha concentration and phospholipid transfer activities during late gestation and newborn period. The concentration of PITP alpha in type II cell cytosol measured by enzyme-linked immunosorbent assay (ELISA) increased during late fetal gestation to 2.2-fold adult levels and declined 41% during the first postnatal day. However, compared to whole adult lung cytosol, type II cell cytosol was not significantly enriched with PITP alpha. Phospholipid transfer activities were determined by a vesicle-rat lung membrane transfer assay. In adult lung, transfer activities for all the phospholipids were enriched in adult type II cell cytosol compared to whole lung cytosol (phosphatidylglycerol [PG], 12.5-fold; phosphatidylinositol [PI], 9.2-fold; phosphatidylcholine [PC], 6.5-fold; and phosphatidylethanolamine [PE], 6.6-fold; P < .05 in each case). The rate of phospholipid transfer in type II cell cytosol increased during late fetal gestation to levels 4.9 (PG), 3.7 (PI), and 2.8 (PC) times greater than adult levels. In cytosol from cells from different stages, the order of transfer rate was PG > PI > PC > PE. PITP alpha immunodepletion of adult type II cytosol did not significantly affect phospholipid transfer activities, suggesting that other PLTPs are responsible for the majority of the observed transfer activities in these cells. Developmental increases in PITP alpha concentration and other PLTPs parallel developmental changes in type II cell surfactant phospholipid metabolism, suggesting a possible role of these transfer proteins in the unique function of the type II cell.     

Quantitation of phosphatidylcholine secretion in lung slices and primary cultures of rat lung cells

Rat lung slices and isolated rat lung cells were used to study the secretion of phosphatidylcholine by the lung in vitro. The rate of incorporation of [(3)H]choline by lung slices was 20-fold greater than by liver slices and 4-fold greater in lung cells compared to confluent skin fibroblasts. Labeling lung slices or cells with [(3)H]choline for up to 8 hr failed to reveal a significant amount of labeled phosphatidylcholine in the medium of either system compared to the medium from liver slice or fibroblast controls. Labeling of isolated lung cells for up to 24 hr, with or without 10% fetal calf serum, also showed no significant difference in the amount of labeled phosphatidylcholine in the medium compared to control fibroblast cultures. Washing labeled lung slices or cells with a nonlysing concentration of Triton X-100 (0.05%) did not selectively release labeled phosphatidylcholine, indicating that any secreted phosphatidylcholine did not adhere to the surface of the lung slices or cells. Experiments were performed to determine whether the small amount of phosphatidylcholine in the medium and detergent-released phosphatidylcholine was similar to the tissue and cell phosphatidylcholine. The saturated fatty acid composition of the phosphatidylcholine released by Triton X-100 and in the medium (from lung slices) was identical to that of the tissue phosphatidylcholine. In addition, the relative labeling rates of the phospholipids released by Triton X-100 and in the medium (labeled with [(14)C]glycerol) were identical to those of the tissue and cell phospholipids. Based on these results, we conclude that phosphatidylcholine is not secreted by lung slices and lung cells in large amounts compared to controls. The implication of these data is that pulmonary surfactant material may actually not be secreted by the lung in vitro, and perhaps in vivo, in the manner that is currently generally accepted.     

Use of a new gas chromatograph isotope ratio mass spectrometer to trace exogenous 13C labelled glucose at a very low level of enrichment in man

Summary The use of ¹³C labelled glucose in human metabolic studies has been limited by the high cost of the tracer and the problems of measuring low ¹³C isotopic abundance in plasma glucose. In the present work we describe a new gas chromatograph-isotope ratio mass spectrometer allowing the measurement of a 0.001 atom % increase in ¹³C abundance over baseline, on a nanomole glucose sample. Studies were performed in rats and in human subjects. The rate of glucose appearance in 24 h fasted rats using D-[1-¹³C] glucose as tracer and analysed by this new method was found to be 10.4±0.7 mg·kg^–1· min^–1, a value 21% lower than that found using D-[6,6-²H₂] glucose as tracer (13.1±1.1 mg· kg^–1· min^–1) analysed by classic gas chromatography-mass spectrometry. The new method was also used to trace, in combination with D-[6,6 ²H₂] glucose, the metabolic fate in human subjects of two oral glucose loads (0.5 g· kg·^–1), 1 g· kg ·^–1) labelled with 0.1% D-[U-¹³C] glucose. During the six hours following the glucose load, it was found that total glucose appearance was 0.97±0.04 g· kg·^–1 and 1.2±0.04 g· kg·^–1, exogenous glucose appearance was 0.51±0.02 g· kg·^–1 and 0.84±0.04 g· kg·^–1, endogenous glucose production was 0.44±0.04 g· kg·^–1 and 0.35±0.06 g·kg·^–1 after the 0.5 and 1 g·kg·^–1 load respectively. These values are similar to those reported using glucose labelled with radioactive isotopes. These results show that reliable kinetic parameters of glucose metabolism can be determined, without health hazard, in humans, at low cost, using ¹³C labelled glucose analysed with a new gas chromatograph-isotope ratio mass spectrometer.     

In vitro glucose metabolism and lipid biosynthesis in bovine ventricular valves

In vitro oxygen uptake, pathways of [U-¹⁴C] glucose degradation and lipogenesis in the mitral and tricuspid valve of normal bovine heart were compared. In the mitral valve the oxygen consumption, ATP/ADP ratio, lipid content and the amounts of [¹⁴C]-glucose and [¹⁴C]-acetate incorporated into total lipids per mg DNA were higher, while lactate production and NADH/NAD ratio were lower, than those found in tricuspid valve. Triglycerides and phospholipids represented the largest lipid fractions in the mitral and tricuspid valve, respectively, and contained about 60% of the radioactivity incorporated into total lipids, but the highest relative rate of synthesis in the mitral and tricuspid valve was calculated to be for phospholipids and triglycerides, respectively. The bulk (94 to 98%) of [¹⁴C]-glucose incorprated into phospholipids and triglycerides by ventricular valves was found in the glycerol moiety. Incorporation of [¹⁴C]-glucose into fatty acids was markedly lower in the tricuspid than in the mitral valve. In the mitral valve the synthesis of 16 : 0 fatty acid from [I-¹⁴C] acetate proceeded de novo while in the tricuspid valve by a combination of de novo synthesis and chain elongation.     

Effects of visceral adiposity on glycerol pathways in gluconeogenesis

ObjectiveTo determine the feasibility of using oral ¹³C labeled glycerol to assess effects of visceral adiposity on gluconeogenic pathways in obese humans.Research Design and MethodsObese (BMI ≥ 30 kg/m²) participants without type 2 diabetes underwent visceral adipose tissue (VAT) assessment and stratification by median VAT into high VAT-fasting (n = 3), low VAT-fasting (n = 4), and high VAT-refed (n = 2) groups. Participants ingested [U-¹³C₃] glycerol and blood samples were subsequently analyzed at multiple time points over 3 h by NMR spectroscopy. The fractions of plasma glucose (enrichment) derived from [U-¹³C₃] glycerol via hepatic gluconeogenesis, pentose phosphate pathway (PPP), and tricarboxylic acid (TCA) cycle were assessed using ¹³C NMR analysis of glucose. Mixed linear models were used to compare ¹³C enrichment in glucose between groups.ResultsMean age, BMI, and baseline glucose were 49 years, 40.1 kg/m², and 98 mg/dl, respectively. Up to 20% of glycerol was metabolized in the TCA cycle prior to gluconeogenesis and PPP activity was minor (< 1% of total glucose) in all participants. There was a 21% decrease in ¹³C enrichment in plasma glucose in the high VAT-fasting compared with low VAT-fasting group (p = 0.03), suggesting dilution by endogenous glycerol. High VAT-refed participants had 37% less ¹³C enrichment in glucose compared with high VAT-fasting (p = 0.02). There was a trend toward lower [1,2-¹³C₂] (via PPP) and [5,6-¹³C₂]/[4,5,6-¹³C₃] (via TCA cycle) glucose in high VAT versus low VAT groups.ConclusionsWe applied a simple method to detect gluconeogenesis from glycerol in obese humans. Our findings provide preliminary evidence that excess visceral fat disrupts multiple pathways in hepatic gluconeogenesis from glycerol.     

Effects of antiulcer drugs on phosphatidylcholine synthesis in isolated guinea pig gastric glands

To better understand phosphatidylcholine synthesis in the stomach, we isolated guinea pig gastric glands and examined their [³H] choline incorporation into phosphatidylcholine in response to either antiulcer drugs such as geranylgeranylacetone (GGA) and H₂-receptor antagonists or agents that cause phosphatidylcholine synthesis in other tissues. [³H]Choline incorporation was stimulated by GGA, palmitate, and 12-O-tetradecanoylphorbol-13-acetate (TPA). Dibutyryl cyclic-AMP had no effect. By contrast with GGA, famotidine, ranitidine, and cimetidine equipotently inhibited [³H] choline incorporation into phosphatidylcholine. GGA, palmitate, and TPA increased phosphatidyl-[³H] choline and decreased phosphoryl-[³H] choline as compared with control in tissues that had been pulsed with [³H] choline. On the other hand, no more decrease in [³H] choline incorporation at chase periods was observed in pulse-labeled glands in response to each H₂-receptor antagonist. The particulate fraction of glands that had been incubated with GGA or palmitate had more CTP-phosphocholine cytidylyltransferase activity than that of glands incubated without agents. A decrease in choline kinase activity was not observed in the cytosolic fraction of glands that had been incubated with cimetidine. These results suggest that GGA and palmitate stimulate phosphatidylcholine synthesis by activating cytidylyltransferase, and H₂-receptor antagonists may affect phosphatidylcholine synthesis by inhibiting choline uptake in the gastric glands.     

Human Platelets Have Cholesteryl Ester Hydrolytic Activity Toward Plasma High Density Lipoproteins

Human platelet cholesteryl ester hydrolytic (CEH) activity was determined toward high density lipoprotein (HDL) labelled with cholesteryl [1-¹⁴C] oleate resulting in esterilkation of [l-¹⁴C] oleate to platelet phospholipid. The observed CEH activity was enhanced by 100 nM prostacyclin (PGI₂), inhibited by 500 μM 2′, 3′ dideoxyadenosine (DDA), but unaffected by 100 mM chloroquine diphosphate. The CEH activity may represent a mechanism for delivery of other unsaturated fatty acids from HDL to platelets with subsequent modification of the fatty acid composition of platelet phospholipids and potential modification of platelet reactivity.     

Role of myo-inositol in impairment of fetal lung phosphatidylglycerol biosynthesis in the diabetic pregnancy: physiological consequences of a phosphatidylglycerol-deficient surfactant in the newborn rat

To test the hypothesis that the deficit of fetal lung surfactant phosphatidylglycerol (PG) in diabetic pregnancies was due to increased plasma myo-inositol, lung PG content and plasma myo-inositol level were compared in fetuses of streptozotocin-diabetic rats and in fetuses of rats injected with myo-inositol during the 4 last gestational days. An inverse linear correlation was established between circulating myo-inositol and lung phosphatidylglycerol content, including data from fetuses of diabetic rats, which is consistent with the hypothesis. Changes in phospholipid synthetic rates were estimated in fetuses of rats given myo-inositol by measuring incorporation of labelled glycerol on a six hour period on the 21st gestational day, after i.v. injection to the mother. Incorporation into PG was 2.5 times smaller but incorporation into PI or PC were not modified. Pulmonary function in PG-deficient newborns of rats given a high-dosage myo-inositol was assessed by pressure/volume measurements on the lung in situ and by measurement of oxygen tension in aortic blood. Opening pressure of alveoli for lung inflation was increased and blood oxygenation was reduced (30%) in newborns with PG-deficient surfactant as compared with controls, thus suggesting an important physiological role for surfactant PG at birth.     

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.