Adrenergic Receptors in the Mechanism of Regulation of Mitochondrial and Cytoplasmic Enzymes of Cardiomyocytes by Catecholamines.

We studied the role of adrenoceptors in the regulation of activity of mitochondrial and cytoplasmic enzymes in cardiomyocytes by catecholamines and their metabolites. Different types of adrenergic receptors (AR) agonists acting either on both α- and ß-AR or selectively on α- or ß-AR, as well as quinoid metabolites of catecholamines were used. It was found that the activating effect of ß-AR agonist isadrin (isoproterenol) on succinate dehydrogenase of the mitochondria in the heart is prevented by ß-adrenergic blockade. The activating effect of dopamine, epinephrine, and isoproterenol on cytochrome C-oxidase and the inhibitory effect of dopamine, norepinephrine, epinephrine, and isoproterenol on Mg-activated ATPase was not mediated by adrenoreceptors. Hormones of the sympathoadrenal system epinephrine, dopamine, norepinephrine, isoproterenol, and catecholamine metabolites (adrenochrome and adrenoxyl) modulating activity of the respiratory chain enzymes of mitochondria in the heart regulate the processes of tissue respiration by transferring mitochondria into a state of "loose" phosphorylation and respiration coupling. Epinephrine as a ß-AR agonist increased activity of cytosolic enzymes catalyzing metabolism of purine nucleotides (adenosine deaminase and AMP deaminase), enzymes of antioxidant defense (glutathione peroxidase and catalase), and the level of malondialdehyde and diene conjugates. ß-AR blockade with metoprolol abolished the activating effect of epinephrine on glutathione reductase, glutathione peroxidase, and catalase and reduced the level of malondialdehyde and diene conjugates.

[Metabolic effects of combined introduction of adrenalin and blocker of methanoprolol beta-adrenophyleters]. / Metabolicheskie éffekty sochetannogo vvedeniia adrenalina i blokatora beta-adrenoretseptorov metoprolola.

The effect of combined administration of adrenaline (0.4 mg/kg, i.p.) and b1-blocker metoprolol (25 mg/kg) on the activity of glutathione peroxidase (GPO), glutathione reductase (GR), catalase, adenosine deaminase (AD), AMP deaminase (AMPD), 5¢-nucleotidase (5¢N), on the level ofmalonic dialdehyde (MDA) and conjugated dienes (CD) was investigated. In blood adrenaline administration to animals caused an increase in the activity of AMPD, AD, 5¢N and GPO, and the increase the level of CD in the blood increases. Metoprolol caused a more pronounced increase in the activity of blood AMPD, AD, 5'N and the amount of CD. In contrast to adrenaline, metoprolol decreased the MDA level of, and decreased the activity of GPO and catalase. Combined administration of metoprolol and adrenaline to animals was accompanied by an increase in the activity of AD, AMPD, 5¢N, a decrease in the activity of GR, GPO, catalase, and a decrease in MDA in the blood. In the heart, adrenaline injection was accompanied by an increase in the MDA level, a decrease in 5¢N activity and an increase in the ratio of the activities of the enzymes AD+AMPD/5¢N. Metoprolol injection reduced MDA and CD levels and the activity of GR and GPO. The combined administration of metoprolol and adrenaline in the heart was accompanied by activation of AD, AMPD and 5¢N, and a decrease in the amount of MDA and CD, and a decrease in the activity of GR, GPO, and catalase. In the liver adrenaline caused an increase in MDA and DC levels, activation of catalase, AD, AMPD, and 5¢N. Metoprolol caused a decrease in MDA and CD levels and activity of catalase and GPO, an increase in the activity of AD and AMPD in the liver. Combined administration of adrenaline and metoprolol reduced manifestations of the heart and liver oxidative stress response as compared with administration of adrenaline alone.

[Features of influence adenosine, AMP and hyperadrenalinemiya on the immune status, metabolic enzymes of purine nucleotides and the antioxidant defense system]. / Osobennosti vozdeistviia adenozina, AMP i giperadrenalinemii na immunnyi status, fermenty metabolizma purinovykh nukleotidov i sistemu antioksidantnoi zashchity.

Administration of a large dose of adrenaline (4 mg/kg 60 min before analysis) increased blood levels of total leukocytes, lymphocytes, decreased T-cell suppressors, leukocyte migration inhibition reaction (LMIR) and NBT test, but increased the level of conjugated dienes (CD). Administration of AMPand adenosine increased levels of total leukocytes, lymphocytes, T- lymphocytes, T-helpers, decreased the level of malondialdehyde (MDA), LMIR, and T-cell suppressors. Sympathetic hyperactivation induced by administration of a large dose of adrenaline (4 mg/kg 60 min before analysis) was accompanied by an increase in heart and liver activities of glutathione peroxidase (GPx), catalase, AMP deaminase (AMPD), and adenosine deaminase (AD). Administration of AMP or adenosine caused a decrease in activities of glutathione reductase (GR), GPx, catalase, a decrease in the MDA level and an increase in activities of AMPD and AD in the heart. In the liver AMP and adenosine also caused a decrease in activities of glutathione reductase (GR), GPx, a decrease in the MDA level and an increase in activities of AMPD and AD. The data obtained suggest that administration of adrenaline, AMP, and adenosine influences activity of enzymes involved in purine nucleotide metabolism. However, in contrast to adrenaline, administration of AMP or adenosine does not provoke stress reaction.

[Glutathione redox system, immune status, antioxidant enzymes and metabolism of purine nucleotides in hypothyroidism].

The immune status, components of the glutathione redox system, the activity of antioxidant enzymes and metabolism of purine nucleotides have been investigated in animals with experimental hypothyroidism. On day 8 after an increase in the number of leukocytes, lymphocytes, T-helpers and T-suppressors as well as increased number of B-lymphocytes was found in blood of thyroidectomized rats. This was accompanied by decreased activity of adenosine deaminase (AD), AMP-deaminase (AMPD), and 5'-nucleotidase (5'N) in blood, but the ratio of enzyme activity AD/AMPD increased. These changes in the activity of enzymes, involved in purine catabolism can be regarded as increased functional relationships between T and B lymphocytes in hypothyroidism. The functional changes of immune system cells were accompanied by increased activity of glutathione peroxidase (GPx), a decrease in the activity of superoxide dismutase (SOD), glutathione reductase (GR) and the ratio GH/GPx. Thyroidectomized rats had increased amounts of total, oxidized (GSSG) and reduced glutathione (GSH), but the ratio GSH/GSSG decerased as compared with control animals. In the liver, hypothyroidism resulted in activation of SOD, GPx, decreased activity of GR and decreased ratio GR/GPx. At the same time, the levels of total, oxidized, and reduced glutathione increased, but the ratio GSH/GSSG as well as activities of enzymes involved in purine nucleotide metabolism ratio (and their ratio 5'N/AD + AMPD) decreased. All these data suggest a functional relationship of the glutathione redox system not only with antioxidant enzymes, but also activity of enzymes involved purine nucleotide metabolism and immune status.