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Serotonin reduces the behavior tolerance of Caenorhabditis elegans of the N2 wild-type strain (swimming induced by the mechanical stimulus) to a temperature of 36 degrees C. The sensitivity to the serotonin influence on the behavior thermotolerance remains intact in strains with null mutations of mod-1 (ok103) and ser-1 (ok345) serotonin receptor genes, and is almost completely lost in the ser-4 (ok512) strain with null mutation in the gene of the SER-4 serotonin receptor, which is a homologue of 5-HT1 mammalian serotonin receptor. In addition, nematodes of the ser-4 (ok512) strain have high behavior thermotolerance in the absence of the exogenous serotonin compared to the N2 strain. These data indicate the involvement of the ser-4 gene in the serotonin regulation of the tolerance of C. elegance nervous system functions to hyperthermia.

The lines of Caenorhabditis elegans displaying low (LT) and high (HT1, HT2, and HT3) thermotolerance were obtained from the wild line N2 by artificial selection for thermostability of locomotion and by natural selection in laboratory for thermotolerance of fertility under tolerable environmental temperature elevation. All these lines are new genetic variants that emerged during the experiment. The worms of lines HT2 and HT3 displayed an elevated upper temperature limit for reproduction (from 26 to 27.5 degrees C), thermostability of locomotion at 36 degrees C, and survival at 37 degrees C as compared with the line N2. The results have demonstrated that adaptation of C. elegans to high temperatures is an appropriate laboratory model for studying the mechanisms involved in the evolution of thermotolerance of poikilothermic Metazoa.

The pore with an effective diameter of 6.0 A is a Ca(2+)-channel of the inner mitochondrial membrane. Transport of nonelectrolytes through the pore is inhibited by ruthenium red, a specific Ca2+ transport inhibitor, and by polyanions which bind to the positively charged regions in the pore localized on the outer side of the inner mitochondrial membrane. The selectivity of Ca2+ ion transport into intact mitochondria is due to the binding of Ca2+ ions by the glycoprotein at the mouth of the pore as well as to electrostatic interactions of monovalent cations (electrostatic repulsion) and Cl- ions (strong binding) with the positively charged region of the ion-selective filter of the pore. Under normal conditions SCN- and NO3- ions are transferred through the pore at a high rate. Removal of Mg2+ ions and the rise in pH diminish the electrostatic repulsion of the monovalent cations and Cl- ions from the positively charged region of the pore. Depending on conditions, the pore can function as a monovalent ion transport system or as a mechanism of Cl- ion transfer through the inner mitochondrial membrane.

Small concentrations of low molecular weight modulators of the functional state of rat liver cytoplasm mitochondria, which uncouple oxidative phosphorylation, induce phosphate-dependent transport of potassium and hydrogen ions. In contrast, high concentrations of these compounds induce nonspecific transport of monovalent cations and sucrose (K+ > H+ > Na+ > or = Li+ > sucrose). The effect of cytoplasmic modulators on oxidative phosphorylation and permeability of the inner mitochondrial membrane in inhibited by cyclosporin A and controlled by physiological concentrations of Ca2+. It is assumed that ion transport across the inner mitochondrial membrane in the presence of cytoplasmic modulators is implemented by the same cyclosporin-sensitive transport system which in damaged mitochondria functions as a nonspecific pore.

Studies of swelling of rat liver mitochondria in isoosmotic solutions of nonelectrolytes in the presence of respiration inhibitors revealed that submicromolar concentrations of Ca2+ increase the diameter of pores in the inner mitochondrial membrane--from 5.5-6.0 A (10(-8) M Ca2+) up to 7.5 A (3 x 10(-7) M Ca2+) and 8.0-8.5 A (6 x 10(-7) M Ca2+); these increases are prevented by cyclosporin A. The inner mitochondrial membrane with an effective pore diameter of 7.5 A is readily permeable for potassium but not for sodium ions, although with an increase in the effective pore diameter up to 8.0-8.5 A the selectivity of the K(+)-Na+ channel decreases. A conclusion is drawn that in the presence of submicromolar concentrations of Ca2+ the conductivity of the cyclosporin-sensitive pore for monovalent cations increases in the following order: K > Na > Li.

In vivo thyroid hormones control the binding to mitochondria of low molecular weight water-soluble cytoplasmic mediators that are capable to induce oxidative phosphorylation uncoupling, by increasing the sensitivity of mitochondria to the effects of these mediators. In hyperthyroid rat liver mitochondria cytoplasmic mediators stimulate the phosphate-dependent transport of K+ and H+ in a greater degree than in liver mitochondria of control rats. The increase in the oxidative phosphorylation uncoupling by cytoplasmic mediators is one of mechanisms of thermogenesis stimulation by thyroid hormones.

A water-soluble thermostable factor from rat liver cytoplasm whose activity decreases during starvation, causes the uncoupling of oxidative phosphorylation and stimulates pyruvate oxidation in rat liver mitochondria. The activity of this factor is insensitive to pronase treatment. Gel filtration and ion-exchange chromatography resulted in three low molecular weight water-soluble fractions which bear a negative charge at alkaline values of pH and induce electrophoretic transport of K+ and phosphate across the inner mitochondrial membrane. The effect of this factor on K+ transport is manifested at pH less than or equal to 7.0, that on phosphate transport-at pH 6.5-7.6.

Cytoplasmatic glycoprotein previously shown to be an inhibitor of mitochondrial membrane permeability for oxidation substrates inhibits in-vitro gluconeogenesis from pyruvate, lactate, succinate, alpha-ketoglutarate and glutamate in slices of the renal cortical layer. The inhibition was reduced with Ca2+ concentration increase in the incubation medium from 0.02 to 2 mM.

Cytoplasmatic glycopeptide-induced bicarbonate ion electrogenic transport through mitochondrial membrane has been studied. Glycopeptide, described earlier as a factor increasing inner mitochondrial membrane permeability for phosphate ions, has been also shown to induce bicarbonate ion electrogenic transport through inner mitochondrial membrane. HCO3- ion transport, induced by cytoplasm glycopeptide is realized by pH-dependent pore. The interrelation of cytoplasm glycopeptide with mitochondria is regulated by mitochondrial energization.

Upon starving and muscle work the activity of an insulin-dependent cytoplasmic regulator (IDR) in the rat liver has been demonstrated to be lowered. This is one of the mechanisms of glycogenolysis and gluconeogenesis stimulation. Rapid increase in IDR activity in the heart and liver has been recorded in the period of recovery after swimming, with the increase being more intense in the heart. It has been shown that in the heart the resynthesis of glycogen proceeds more rapidly than in the liver. Therefore, the rate of glycogen resynthesis by the liver and heart correlates with IDR activity.

The manifestation of Ca2+/2H+ antiporter activity in rat liver mitochondria was shown to be inhibited in thyroidectomy and stimulated in hyperthyroidosis. Experiments with measuring the kinetics of the swelling of deenergized mitochondria in isoosmotic solutions Ca (NO3)2, pH 8.1 demonstrated inhibition of the swelling of liver mitochondria during thyroidectomy and stimulation because of administering thyroid hormones in vivo. During thyroidectomy, the phosphate-induced swelling of rat liver mitochondria was powerfully inhibited. Meanwhile administration of thyroxine to rats stimulated the swelling of mitochondria.

It was shown that a factor from the thyroxine-injured mitochondria caused inhibition of mitochondrial swelling in isotonic KNO3 and NH4NO3 solutions in the presence of rotenone. These data were interpreted as permeability inhibition for K+ and H+ ions.

Activity of cytoplasmic inhibitor of Ca2+ transport in rat heart mitochondria was studied after total ischemia and incubation of heart homogenates with cAMP. Distinct inactivation of the inhibitor occurred under these conditions. The decrease of the inhibitor activity in ischemic myocardium appears to serve as a compensatory mechanism: 1. pyruvate dehydrogenase and the enzymes of tricarboxylic acid cycle were activated due to increase in Ca2+ concentration in mitochondria, 2. as a result of Ca2+ accumulation in mitochondria the elevated concentration of Ca2+ was decreased in myoplasm, which developed after impairment of plasmatic membranes and of sarcoplasmic reticulum membranes.

The insulin-dependent cytoplasmic factor-regulator (IDR) was shown to inhibit pyruvate and succinate oxidation by the rat liver mitochondria. In view of the fact that insulin increases and adrenaline decreases IDR activity in the liver cytoplasm it is suggested that oxidation of the substrate in mitochondria in vivo is regulated by changes in IDR content in cytoplasm. It was shown that adrenaline-activated oxidation apart from decreased activity of IDR in cytoplasm is induced by a different mechanism not related to IDR content.

A thermostable low molecular weight glycopeptide containing syalic acids, which uncouples mitochondrial oxidative phosphorylation, has been detected, isolated and purified from rat liver cytoplasm. In the presence of the glycopeptide, oxidative phosphorylation in rat liver mitochondria is uncoupled by low physiological concentrations of Ca2+, which otherwise do not have any appreciable effect on the mitochondria. Oxidative phosphorylation uncoupling by the glycopeptide is accompanied by an increase of the mitochondrial volume. This process has a limited amplitude and is regulated by changes in Ca2+ concentration in the extramitochondrial space. The glycopeptide has been shown to induce K+ transport across the inner mitochondrial membrane, this effect is enhanced by Ca2+.

Immobilization decreased the activity of insulin-dependent cytoplasmatic regulator in the rat liver. Cessation of the immobilization resulted in increment of insulin--dependent cytoplasmatic regulator activity in liver and diaphragm. After the immobilization the glycogen content is considerably higher in the liver, which seems to be due to an increase in the regulator activity. The restoration after the immobilization leads to a decrease in hypoglycemic action of insulin in vivo and in insulin-dependent cytoplasmatic regulator action in vitro.

Addition of a thermostable cytoplasmic fraction leads to the uncoupling of oxidative phosphorylation of the mitochondria. In hyperthyrosis such an effect manifests itself more powerfully than in the control. Addition of the thermostable cytoplasmic fraction induces electrogenic phosphate transport via the mitochondrial membrane. In hyperthyrosis, the activity of the thermostable inducer of phosphate transport in the cytoplasm increases. The functioning of the phosphate cycle may be the cause of the uncoupling of oxidative phosphorylation of the mitochondria during the disease in question.

In ischemic impairment of liver tissue the activating effect of the cytoplasmic thermostable fraction on the transport of Ca2+ ions was decreased in liver mitochondria. Fast decrease in the cytoplasmic activity occurred also after preincubation of liver homogenate with salt solutions. Inactivation of the cytoplasmic regulator was prevented by addition of EGTA into the homogenate, but Ca2+ showed the opposite effect. The data obtained suggest that high concentration, of Ca2+ in cytosol under conditions of ischemia is responsible for decrease of the cytoplasmic regulator activity.

During thyroidectomy, the stimulating action of the catalytic amounts of a thermostable fraction of rat liver and diaphragm cytoplasm on Ca2+ transport in mitochondria, which indicates the decrease of the activity of an insulin-dependent cytoplasmic regulator (IDR) in insulin target organs. Thyroidectomized rats also manifested a decrease in blood insulin and glucose concentrations. Administration of the physiological doses of thyroxine produced an increase in both blood glucose concentration and IDR activity in the liver and diaphragm of thyroidectomized rats. Experiments with measuring the kinetics of the swelling of deenergized mitochondria in isoosmotic solution of ammonium pyruvate demonstrated the inhibition of liver mitochondrial swelling in thyroidectomized rats.

The activity of the insulin-dependent regulator (IDR) in the thermostable fraction of the cytoplasm isolated from the liver, heart and diaphragm of rats as well as the glycogen level in the liver were estimated. The IDR activity in the insulin target organs and glycogen concentration in the liver were raised in the pregnant well-fed rats; a tendency to their decrease was observed after 24 h starvation. The range of changes between satiation and starvation was much more pronounced in the pregnant rats than in the controls. The IDR activity was also higher in well-fed rats receiving progesterone for 5 days and did not change after a single injection of progesterone. It was concluded that a raised level of progesterone in the blood was one of the reasons for an increase in the IDR activity in pregnant rats. An increase in the IDR activity in the insulin target organs under conditions of insulin resistance induced by pregnancy or progesterone administration testifies to the fact that the binding of insulin with its receptors is not a limiting link in the mechanism of insulin action.