Phospholipids and calcium alterations in platelets of schizophrenic patients.

Alterations in phospholipid metabolism in blood elements have been proposed as the possible biochemical marker of schizophrenia. In the present study, we investigated the composition and membrane distribution of phospholipids in platelets of drug-free schizophrenic patients and controls. We have demonstrated that platelets of drug-free schizophrenics have significantly higher cytosolic Ca2+ levels in comparison with healthy controls. Platelets of drug-free schizophrenic patients have a lower content of phosphatidylinositol (PI). After thrombin activation, PI is the target of phospholipase C instead of phosphatidylinositol 4,5-bisphosphate (PIP2), which is hydrolyzed in platelets of controls. Alterations in the distribution of phospholipids were found in the plasma membrane of platelets of schizophrenic patients. We suggest that alterations in phospholipid metabolism might be evoked by a disturbance of calcium homeostasis in schizophrenic patients.

[Phospholipase A2 in schizophrenia]. / Fosfolipáza A2 u schizofrenního onemocnení.

The objective of the present work was to evaluate on the basis of the authors' data and data in the literature the role of phospholipase A2 in the pathogenesis of schizophrenia. The authors submit available literature pertaining to the problem as well as their own experimental findings. Based on the submitted facts, it cannot be states that phospholipase A2 is a specific marker of schizophrenia.

[ATPase activity, endogenous depression, lithotherapy and electroconvulsive therapy]. / Aktivita ATPáz, endogenní deprese, lithioterapie a elektrokonvulzívní terapie.

The author gives a brief account of the action of ATP-ases in the organism. He describes the effect of different substances on the action of these enzymes, whereby special attention is paid to the action of psychopharmaceutical preparations, incl. lithium salts, on the activity of Na+K(+)-ATP-ase. In the experimental part he investigates the activity of ATP-ases in endogenous depressions in our population, the influence of Li+ and electroconvulsions on these enzymes. The results are consistent with data in the literature. Changes in the ATP-ase activities in the course of treatment imply that these enzymes are not genetic markers of depressions. The different effect of therapeutic preparations on the activity of ATP-ases indicates that influencing ATP-ase activity in relation to depressive conditions cannot be considered causal.

Insulin binding to erythrocytes and fatty acid composition of erythrocyte membrane phospholipids in healthy men.

The relationship between specific insulin binding to insulin receptors on erythrocytes and erythrocyte membrane phospholipid fatty acid pattern was evaluated in 11 healthy men. A significant negative correlation between insulin binding and the proportion of w-6 family essential fatty acids, especially linoleic acid (r = -0.82, p less than 0.01) and arachidonic acid (r = -0.73, p less than 0.05) in erythrocyte membrane was found. On the other hand significant positive correlation between insulin binding and the content of nonessential fatty acids (r = +0.65, p less than 0.05) was seen. Data presented support the hypothesis that the fatty acid composition of membrane phospholipids may modify properties of insulin receptors.

Erythrocyte insulin receptor characteristics and erythrocyte membrane lipid composition in healthy men.

The cell membrane plays an important role in the mechanism of insulin action. To test whether erythrocyte insulin receptor characteristics are related to the erythrocyte membrane lipid composition, 11 healthy volunteers were studied. The relationship between insulin binding to erythrocytes, the number of receptors per cell and the affinity of receptors to insulin on the one hand and total phospholipid fatty acid (FA) composition and cholesterol/phospholipid molar ratio in the erythrocyte membrane on the other hand were evaluated. 1. We found a significant negative correlation between specific insulin binding and the proportion of n-6 essential FA in erythrocyte membrane phospholipids, especially linoleic acid (r = -0.82, p less than 0.01) and arachidonic acid (r = -0.73, p less than 0.05). On the other hand, a significant positive correlation between insulin binding and the proportion of nonessential FA (r = +0.65, p less than 0.05) was seen. Number of receptors per cell and the affinity of receptors were not significantly related to phospholipid FA composition. 2. There was no significant correlation between insulin receptor characteristics and the cholesterol/phospholipid molar ratio in the erythrocyte membrane. The data presented support the hypothesis that the FA pattern of membrane total phospholipids may modify the properties of insulin receptors.

Tricyclic antidepressant binding to lymphocyte membranes and changes during depression.

The binding of [3H]imipramine, its 2- and 4-nitroderivatives and [3H]desmethylimipramine to lymphocyte membranes was determined. IC50 values for drugs and neurotransmitters to inhibit [3H]imipramine binding to lymphocyte membranes were comparable with those for brain and thrombocyte membranes. The number of [3H]imipramine and [3H]desmethylimipramine binding sites increased in depressive patients, whereas the dissociation constants remained unchanged.

Effect of immobilization stress on tricyclic antidepressant binding and serotonin uptake in rats.

Immobilization stress increased the density of imipramine binding sites in platelet and cortical membranes and there was an increased serotonin uptake in platelets. There was a decrease in desipramine binding and noradrenaline uptake in lymphocytes. Our results show that stress acts on the mediator systems in various ways.

Plasma imipramine levels and demethylase activity in the liver of stressed animals.

The steady-state values in rats after a second 14-day period of daily subcutaneous administration of imipramine were the same as during the first period; liver demethylation activity rose for up to 3 days and then returned to normal. The imipramine-binding capacity of the serum, brain myelin, synaptosomes and mitochondria did not alter after repeated administration, but a decrease was found in the red blood cells. Stress (an electric current or immobilization) led to marked reduction of the plasma imipramine level, with a simultaneous increase in liver demethylase activity. Adrenalectomy caused a drop in demethylase activity; stress had no effect either on these values or on imipramine levels.

Distribution of cesium in the organism and its effect on the nucleotide metabolism enzymes.

After the intraperitoneal administration of 0.5 mEq 134 CsCI . kg -1 to mice, the maximum cesium level in the kidney's, heart, lungs and liver was found in the first hour (T 1/2 13 h), in the muscles after 8 h (T 1/2 180 h), in the brain after 24 h (T 1/2 140 h) and in the blood after 24 h. Maximum cesium levels were found in the muscles. Rats excreted about 17% of the administered dose in 24 h and 38% in 144 h. Most of the cesium (about 90%) is excreted in the urine. In rats, equalization of the plasma and RBC cesium levels takes longer than 6h. Cesium transport is not entirely dependent on the ATPase system, as shown by the results given by the crude mitochondrial fraction with a reduced potassium content. Among the various univalent ions studied, the effect of cesium on creatine kinase, 5'-nucleotidase, phosphodiesterase and deaminase activity was the smallest.

[Lithium and nucleotide metabolism in brain tissue]. / Litii i metabolizm nukleotidov v mozgovoi tkani.

The paper is concerned with the influence of lithium on the metabolism of free nucleotides and the main sourse of marcoerges in the cell ATP. It was established that lithium increases the consumption of glucose by the brain tissues of rats and guinea pigs, stimulating the creation of macroegic phosphates. Lithium increases the synthesis of cyclic adenosinmonophosphates (AMP) especially on the background of stimulators of adenylatcyclase, the activity of which is inhibited by lithium and calcium and is not changed under the influence of rubidium. Lithium exerts an inhibiting action on the activity of phosphodiestherase, especially expressed on the background of detergent actions. In experimental conditions it stimulates the formation of inosinmonophosphates from AMP and by this way may change the synthesis of nucleotides in the CNS.

Effect of rubidium, lithium and cesium on brain ATPase and protein kinases.

The authors studied the effect of rubidium, lithium and cesium on the ATPase system and c-AMP protein kinase in brain. They demonstrated that rubidium could replace potassium in the Na+K-ATPase system, whereas lithium and cesium had no effect on this enzyme activity in the absence of potassium. K+-dependent ATPase was activated by even low rubidium concentrations; lithium and cesium inhibited it. None of three (rubidium, lithium and cesium) affected c-AMP protein kinase.