The effect of phenobarbital, ionol and cAMP on the activity of glutathione metabolism enzymes in rodents

The phenobarbital and ionol administration to rats and mice increases considerably the glutathione transferase, glutathione reductase and gamma-glutamyl transferase activities in the liver. The induction of these enzymes has been observed in a number of experiments in the heart and kidney but it was less pronounced. A correlation was established between the induction of glutathione transferase, glutathione reductase and gamma-glutamyl transferase, their changes in mice and rats, phenobarbital and ionol effects. The stimulatory effect of cAMP on glutathione transferase in the liver (and in a number of experiments in the heart) increased against a background of the both agents. The cAMP-dependent activation of glutathione peroxidase was retained in the heart but in some series experiments it disappeared in the liver and kidney. Mechanisms of the long-term (induction) and short-term (cAMP) elevation of the glutathione transferase and glutathione peroxidase activities functioned independently and often in concord. It is suggested that induction of glutathione metabolism enzymes may play an important role in biological effects of ionol.     

Kinetics and regulatory properties of the disulfide reductase enzyme from mouse liver]

Disulfide reductase (DSR) of mice liver supernatant is kinetically demonstrated as associating-dissociating oligomeric protein with positive homotropic cooperativity for the substrate. Cyclic 3',5'-AMP (10(-11)--10(-5) M) activates DSR and increases V, but does not change either [S]0,5, nor nH and does not shift the plot of specific activity versus the enzyme concentration. ATP, GTP, UTP, CTP, protamine, histone, Mg2+, Ca2+, EDTA (but not adenosine, 5'-AMP, 2'3'-AMP, ADP beef serum albumin) activated DSR. The effects of different modifiers are not summed up. Preincubation is essential for the action of the majority of the activators. Heating for 8 minutes at 55 degrees C desensitized completely DSR to all the modifiers without changing its catalytic activity, [S]0,5 and nH values. Possible mechanisms of activation of DSR, especially the involvement of protein kinase, are discussed.     

Regulation of purified NAD-isocitrate dehydrogenase from the pig heart by calcium ions and cAMP-dependent protein kinase

Different cAMP-dependent protein kinases do not phosphorylate homogeneous NAD-isocitrate dehydrogenase (ICDH) and do not change its activity. Ca2+ (3 X 10(-7) = 10(-3) M) activates the enzyme throughout the process of purification including homogeneous enzyme by decreasing the KM for isocitrate. The calmodulin inhibitor trifluoperazine does not change ICDH activation.     

Cyclic AMP activation of respiration of the liver mitochondria in different metabolic states]

cAMP 10(-6) activates the liver mitochondria respiration in all the metabolic states and failed to change or increased the phosphorylation rate in the oxidation of saturating concentration of succinate and isocitrate. Preincubation of mitochondria or homogenate of the liver with cAMP is obligatory for this effect. The fraction V of serum albumin and EDTA did not prevent the effect. Noradrenaline enhanced the mitochondrial respiration only in incubation with the homogenate. The effect of noradrenaline and cAMP was not summed up. Probably the noradrenaline effect was mediated through cAMP. The data obtained are against the decisive role of the respiration and phosphorylation uncoupling or the oxidation substrate accumulation and lead to the assumption on the mitochondria enzymes activation.     

The dynamics of serotonin in tissues in acute hypoxia (the phenomenon and its possible significance]

Serotonin (5HT) decreased in the bone marrow and renal cortex, and hyperserotoninemia developed immediately after one-hour hypoxia. Six-hour hypoxia was followed by an additional decrease of 5-HT in the kidney, medulla, spleen and thymus. Phasic changes of the 5-HT TOOK PLACE at the posthypoxic period. Apparently hypoxia led to the 5-HT mobilization and an increase of its biosynthesis. A possible significance of the 5-HT for the control of hemopoiesis both at the level of the kidney and directly al the level of hemopoietic cells is discussed.     

Choice of quantitative characteristics of a radiation modifier affinity and the range of its pharmacological action (minireview)]

On the basis of the literature the necessity of using not only DMF and maximal protective or sensitizing effects, but also the affinity and the range of the pharmacological action of radiation modifiers is argued. The affinity is worth while to expressed as ED50 (the dose that produces a half of the maximal effect), and the range of the pharmacological action as a therapeutic index K = LD50/ED50.