Prostaglandins and sleep. Awaking effect of prostaglandins and sleep pattern of essential fatty acids deficient (EFAD) rats.

The experiments were carried out to investigate the effects of prostaglandins (PGs) on the sleep pattern in the cat, and in normal and EFAD rats. The data indicate that the duration of slow wave sleep (SWS) was significantly longer in EFAD rats compared with the normal rats. However, no difference in the REM sleep was observed between the two groups. Intraventricular (i.vc. )administration of PGE1, PGE2 and PGF2alpha increased wakefulness without a significant alteration of REM sleep. PGE1 administered i.vc. did not alter the duration of SWS or REM sleep in the chronic cat, but induced ponto-geniculo-occipital (PGO) waves (spikes) which are the phasic phenomenon of REM sleep. The fact that previous administration of 5-hydroxytryptophane abolished the PGE1-induced PGO spiking, might indicate that this drug triggered the spikes mainly via the functional inhibition of the serotonergic system.     

The role of essential fatty acids and prostaglandins in cercarial penetration (Schistosoma mansoni)

We used rat skin membranes to test the putative role of prostaglandins (PG) and essential fatty acids (EFA) in the penetration response of Schistosoma mansoni cercariae. To examine the effects of EFA on cercarial penetration an EFA-deficient rat model was used. Dams were fed an EFA-deficient diet during lactation and the pups were weaned to this diet. Cercarial penetration of EFA-deficient rat skin membranes was not reduced from control levels until 12 wk on the diet. At this time a decrease of 64.3% was observed. This decrease remained constant up to 16 wk, after which the study was terminated. Other normal rats were treated with 20 mg/kg ibuprofen, a PG inhibitor, to examine the role of PG in the penetration response. Treated rat skin contained a mean of 2 micrograms ibuprofen per 30 mm3 of skin (25-mm skin disc) at 1.5 hours post-injection. Skin from treated rats inhibited penetration by over 81%. These studies indicate that skin EFA and PG may have a critical role in the completeness of penetration by cercariae through the skin, although it is not clear whether cercarial or host PG are involved in the penetration response.     

Biosynthesis of phosphoglycerides in skeletal muscle in control rats and in rats deficient in essential fatty acids.

1. The specific radioactivities of individual molecular species of phosphoglycerides in the skeletal muscles of control rats and of rats deficient in essential fatty acids have been determined 3 h after intraperitoneal injection of ortho[32P] phosphate. 2. It has been demonstrated that the high average specific radioactivity of phosphoglycerides in muscles of rats deficient in essential fatty acids is due to both increased amounts and increased turnover of 1-palmitoyl-2-oleoyl phosphatidylcholine and phosphatidylethanolamine. 3. The 1-stearoyl-2-arachidonoyl phosphatidylcholine was found to turn over faster than the 1-palmitoyl-2-arachidonoyl species. In rats deficient in essential fatty acids, the 1-stearoyl-2-(5,6,11-eicosatrienoyl) phosphatidylcholine turned over more rapidly than the 1-palmitoyl-2-(5,8,11-eicosatrienoyl) species. Both findings are in constant with similar findings for liver.     

The proportions of different lecithins in the livers of rats deficient in essential fatty acids

1. Lecithin was prepared from the livers of rats deficient in essential fatty acids and analysed by means of countercurrent distribution. Thin-layer chromatography showed that only lecithin was present. 2. The distributions of phosphorus and the fatty acids at the 3 and 2 positions were determined. 3. It has been shown that 26% of the fatty acids in the 3 position were unsaturated and that most of the Delta(5,8,11)-eicosatrienoic acid and the arachidonic acids occur as the stearoyl or oleoyl lecithins.     

Inhibition of sheep vesicular gland oxygenase by unsaturated fatty acids from skin of essential fatty acid deficient rats

Unsaturated fatty acids present in the lipids of essential fatty acid (EFA)-deficient rats were found to inhibit the oxygenase activity of sheep vesicular gland in an instantaneous, reversible manner. However, competitive inhibition by high levels of these acids cannot account fully for the reported loss of prostaglandin synthetic capacity of these EFA-deficient animals. A similar competitive inhibition pattern was observed with several anti-inflammatory drugs tested, whereas others also exhibited a time-dependent destructive effect on the oxygenase of the sheep vesicular gland. The relative effectiveness of these drugs in treating inflammations of the skin paralleled their effects on the vesicular gland oxygenase.     

Non-shivering thermogenesis and brown adipose tissue activity in essential fatty acid deficient rats.

The effects of essential fatty acid (EFA) deficiency on energetic metabolism and interscapular brown adipose tissue (BAT) activity were examined in the cold acclimated rat. Weanling male Long-Evans rats were fed on a low fat semipurified diet (control diet, 2% sunflower oil; EFA deficient diet, 2% hydrogenated coconut oil) for 9 weeks. They were exposed at 5 degrees C for the last 5 weeks. In EFA deficient rats, compared to controls, growth retardation reached 22% at sacrifice. Caloric intake being the same in the two groups, it follows that food efficiency was decreased by 40%. Resting metabolism in relation to body surface area was 25% increased. Calorigenic effect of norepinephrine (NE) in vivo (test of non-shivering thermogenesis) underwent a marked decrease of 34%. BAT weight was 21% decreased but total and mitochondrial protein content showed no variation. A 26% increase in purine nucleotide binding per BAT (taken as an index of thermogenic activity) was observed, suggesting that the enhancement in resting metabolism observed was mainly due to increased BAT thermogenesis. However, BAT mitochondria respiratory studies which are more direct functional tests showed a marked impairment of maximal O2 consumption of about 30% with palmitoyl-carnitine or acetyl-carnitine (both in presence of malate) or with alpha-glycerophosphate as substrate. It is likely that this impaired maximal BAT oxidative capacity may explain the impaired NE calorigenic effect in vivo. A possible increase in mitochondrial basal permeability is also discussed.     

Selective incorporation of n-3 and n-6 fatty acids in essential fatty acid deficient rats in response to short-term oil feeding

Essential fatty acid deficient male Sprague Dawley rats were fed for 7 days a fat-free semi-synthetic diet supplemented with 10% by weight of different oil supplements. The oil supplement was a mixture of olive, safflower and linseed oils prepared at different proportions so the dietary n-9/n-6/n-3 ratios were approximate 2/1/1, 1/2/1, 1/1/2, and 1/1/1. The fatty acid compositions of plasma and liver lipids were then examined. Our results show polyunsaturated n-6 and n-3 fatty acids were selectively incorporated into plasma and liver phospholipids, and also into plasma cholesteryl esters. A preferential incorporation of n-6 over n-3 fatty acids into plasma cholesteryl esters and phospholipids was also observed.     

Effects of infusion of some prostaglandins in essential fatty acid-deficient and normal rats

Infusion of 1 mg/kg per day of prostaglandin E(1) (PGE(1)) for 2 and 7 wk failed to correct the dermal signs of essential fatty acid (EFA) deficiency in rats despite the known conversion of EFA to certain prostaglandins. PGE(1) caused no significant changes in serum cholesterol, triglycerides, or phospholipids or in liver neutral lipids in EFA-deficient or normal rats. In normal rats epinephrine-induced lipolysis was greater in fat pads from infused than from untreated rats. The effect on epinephrine-induced lipolysis was greater after the 7 wk infusion than after the 2 wk infusion. The 7 wk infusion also lowered plasma free fatty acid (FFA) concentrations. Infusion of PGE(2) and PGF(2alpha) in combination for 4 wk had no significant effect on either dermal signs of EFA deficiency, lipolysis, or plasma FFA concentrations.