A fast in vitro effect of glucocorticoids on hepatic lipolysis.

A fast and direct effect of dexamethasone on liver metabolism is reported. In the perfused rat liver, addition of dexamethasone directly to the perfusate is followed by an increase in the level of free fatty acids (FFA) and glycerol. These effects of dexamethasone are evident within 30 minutes of hormone administration. The response to dexamethasone in livers from normal and adrenalectomized rats is similar. While dexamethasone and glucagon both had a lipolytic effect, these effects are not additive.

Essential fatty acids (EFA) deficiency and liver mitochondria.

2 dietary fats, namely, hydrogenated coconut oil and safflower seed oil were fed at 20% levels to weanling male albino rats for a period of 2 months after which the animals were sacrificed and oxidative phosphorylation measured in liver mitochondria. This ratio was more in the unsaturated-fat-fed group of rats compared to the saturated-fed ones for glutamate and malate; in the case of succinate no such change was noticed.

Cholesterol esterification activities in the intestines and pancreas of the albino rat.

Cholesterol esterification activities in intestines and pancreas are much greater with unsaturated fatty acids than with the saturated ones; the maximum activity is with arachidonic acid in intestines and with oleic acid in pancreas. The pancreatic cholesterol esterification activity is higher than the intestinal one.

Effect of dietary fats on oxidative phosphorylation and fatty acid profile of rat liver mitochondria.

Hydrogenated coconut oil or safflower seed oil were fed at 20% levels to weanling male albino rats for 2 months. The fatty acid patterns of the liver homogenates, mitochondria and the microsomes were determined by gas chromatography as were also the fatty acid patterns of the liver cholesterol esters and the phospholipids. The mitochondrial phospholipids were fractionated by thin layer chromatography and the fatty acid moieties of the individual phospholipids were screened on a gas chromatograph. The oxidative phosphorylation in the liver mitochondria was determined using glutamate, malate and succinate as substrates. The liver fatty acid pattern, especially that of the subcellular particles, seemed to be dependent upon the dietary fat. The fatty acid composition of the mitochondrial phospholipids varied with the dietary fat. Oxidative phosphorylation for glutamate and malate was higher in the group fed safflower oil compared to that in the group fed saturated fat; in the case of succinate, no such difference was noticed. These results suggest that the changes in the phosphorylation capacity are due to the changes in the mitochondrial phospholipids which reflect the composition of the dietary fat.

Relative halothane accumulation in brain subcellular membranes in vitro.

The accumulation of halothane in brain homogenates was compared with halothane accumulation in brain during inhalation at anesthetic and subanesthetic levels. Anesthesia is achieved at a tissue concentration well below the halothane solubility in brain tissue. Analysis of halothane in the particulate solids of brain homogenate and in purified subcellular membranes indicates that a membrane constituent (presumably the lipids) acts as an ideal solvent in which halothane is fully miscible. Therefore, membranes offer a local microenvironment in which halothane accumulation deviates from Henry's law. Specifically, we observe that even slight increases of halothane in a saline medium result in a relatively large increase in the concentration of halothane in subcellular membranes suspended in the medium, eventually leading to solvation of the membrane in halothane. This observation offers a ready explanation for the high degree of positive correlation between MAC and lipid solubility and the small difference between anesthetic and lethal concentrations of halothane during inhalation. The rate of halothane increase in myelin exceeded the rate in other brain subcellular membranes, indicating that a major site of halothane localization is within this subcellular membrane.

Halothane accumulation in rat brain and liver.

Halothane concentrations (microgram/g wet weight) was measured in rat brain and liver following exposure to various concentrations of halothane in air. Because of the difficulty of determining the amount of a volatile compound in brain, we analyzed tissue fixed by two different methods. The apparent concentration of halothane in brain was higher following direct decapitation into liquid nitrogen, than after decapitation, removal of fresh tissue, and then freezing. However, the relative effects of altering the inspired concentration were essentially the same in each case. Thus, absolute quantitative accuracy remains a point for discussion; however, we can reach several conclusions regarding the relative accumulation of halothane in brain tissue following various conditions of exposure. Resultant tissue concentrations of halothane were not linearly related to ambient concentrations. Above an inspired concentrations of 1.0%, an increase to 1.5% inspired concentration caused little further increase in the halothane concentration in brain, although the liver concentration increased in proportion to the dose increase. Below an inspired concentration of 0.5%, tissue concentrations were less expected, probably as a result of metabolic degradation occurring at a rate that becomes more noticeable at lower inspired concentrations. Body size was shown to be an important variable affecting the time required for each tissue to reach equilibrium at a given inspired concentration. These data indicate that tissue concentrations at low exposure levels may be less than proportional at dose and that concentrations in small laboratory animals may be expected to exceed values in humans under equivalent conditions of exposure.

Intracellular translocation of myelin proteolipid protein.

Brainstem slices prepared from 22-day-old rats were employed to study the intracellular translocation of radioactively labeled myelin proteolipid protein (PLP). Double-isotope and short pulse-chase procedures allowed us to demonstrate the flux of PLP through nine different subcellular membrane fractions that were isolated on the basis of their particle size and buoyant density. Tagged PLP was rapidly depleted from microsomes, showed transient passage through a number of presumably intermediate membranous pools, and accumulated in myelin. On the basis of the kinetics of PLP labeling and isotope ratios, the membranes can be arranged as they participate in the intracellular translocation of PLP and consistently show a pattern indicating possible precursor-product relationships.

Brain cyclic nucleotide responses to anesthesia with halothane delivered in air or purified oxygen.

Inhalation of either 0.5% or 1.0% halothane in air caused a slight decrease in the cAMP concentration in rat cerebral cortex and cerebellum. During recovery, concentrations returned to normal in 3 h, or less. In contrast, cGMP decreased sixfold in cerebellum, but increased twofold in cortex. Recovery time for cerebellum was several hours. When oxygen was used as the carrier gas for halothane delivery, cAMP in the cortex doubled, in striking contrast to the case with halothane in air. Oxygen alone had no apparent effect. The cGMP effect of halothane delivered in oxygen appeared the same as for halothane in air. Thus, the cAMP effects of brain halothane are related to the enrichment of oxygen.

Brain cyclic nucleotide and energy metabolite responses to subanesthetic and anesthetic concentrations of halothane.

Adult rats were exposed to 0.5, 1.0 and 1.5% halothane, delivered in air, for 1 h. Whole brain 3',5'-cyclic adenosine monophosphate (cAMP) of halothane-exposed rats showed only a slight increase relative to control values. 3',5'-Cyclic guanosine monophosphate (cGMP) was increased significantly in halothane-exposed rats, and the response was directly related to the halothane concentrations. Adenosine triphosphate (ATP) and phosphocreatine (PC) remained unchanged relative to control values. Correspondence of these values to apparent discrepancies in the literature is discussed.

Evidence for a cyclic GMP mechanism in the mediation of hippocampal post-tetanic potentiation.

Correlative electrophysiological and biochemical techniques were used to study hippocampal post-tetanic potentiation in acutely prepared rabbits following stimulation of the medial septal region and contralateral hippocampal field CA3. The results indicate that calcium ions, guanosine-3':5'-monophosphate, and phosphodiesterase inhibitors selectively enhanced the duration of post-tetanic potentiation. Potassium ions selectively enhanced tetanic potentiation. Adenosine-3':5'-cyclic monophosphate suppressed both tetanic and post-tetanic potentiation. The electrophysiological findings were supported by biochemical observations that guanosine-3':5'-monophosphate levels show marked increases following tetanic stimulation of either the medial septal region or contralateral hippocampal field CA3 pathways. The data suggest that a calcium-dependent process in the presence of a guanosine-3':5'-monophosphate mechanism promotes periods of hippocampal pyramidal cell hyperexcitability. The mechanism by which the cyclic nucleotide alters potentiation does not appear to be coupled to a single receptor variety.

Dietary supplementation of undernourished rats with soy or safflower oil: effects on myelin polyunsaturated fatty acids.

Undernourished suckling rats were administered, by gastric intubation, either soy oil (which is rich in both linoleic and linolenic acids) or safflower oil (which is rich in linoleic acid but deficient in linolenic acid) to determine (1) if dietary supplementation would offset the hypomyelination characteristic of the undernourished, developing brain and (2) to compare myelin fatty acids in normal, undernourished, and oil-supplemented rats. Myelin recovery was not increased by supplementation with either oil. The proportions of C22:4 and C22:6 fatty acids were reduced in myelin of the undernourished rats. Undernourished rats supplemented with either soy or safflower oil had higher than normal proportions of polyunsaturated fatty acids (C20:4 and C22:6). The triene-tetraene ratio in the oil-supplemented rats was lower than in normal controls, indicating that the oil-supplemented rats were not deficient in essential fatty acids. No significant differences were observed between the oil-supplemented groups.

Inhibition of cyclic nucleotide accumulation following hippocampal tetanic potentiation: effects of diazepam.

Biochemical studies on the hippocampus of acutely prepared rabbits revealed more than twofold increases in cyclic GMP levels following tetanic potentiation of the pathway from the medial septal region to CA1 pyramidal cells. Diazepam, administered intravenously, prevented the elevation in cyclic GMP levels in this region and also attenuated the post-tetanic potentiation seen following the presentation of trains at frequencies within theta rhythm. The results imply a modulatory role for cyclic nucleotides in the enhancement of pyramidal cell excitability and suggest that the biochemical mechanism for the psychoactive benzodiazepines may well include the suppression of cyclic GMP levels.