[The process of cyclic adenosine-3',5'-monophosphate phosphodiesterase activation by 2',5'-oligoadenylate]. / Issledovanie protsessa aktivatsii fosfodiésterazy tsiklicheskogo adenozin-3',5'-monofosfata 2',5'-oligoizoadenilatom.

The effect of 2',5'-oligoisoadenylate on the activity of cyclic nucleotide (cAMP and cGMP) phosphodiesterase in cell (NIH 3T3) lysate was studied. It was shown that the activation of cAMP phosphodiesterase by 2',5'-oligoisoadenylate occurs via a non-competitive mechanism, i.e. the activator does not affect cAMP binding to phosphodiesterase but increases the rate constant of the reaction product (k2) formation. The kinetic parameters of this reaction, i.e. the values of activation constant, K alpha, and parameter beta characterizing the increase in the enzyme turnover number, were determined. 2'5'-Oligoisoadenylate was shown to cause specific activation of cAMP hydrolysis without affecting the activity of cGMP phosphodiesterase.

A study on the relationship between the interferon enzyme system and the system of cyclic nucleotide metabolism.

In order to study interrelationships between the components of the interferon enzyme system and the cyclic AMP system, NIH 3T3 cells were incubated in the presence of theophylline or adrenaline that cause a rise of intracellular cAMP, respectively, through inhibition of phosphodiesterase of cAMP and activation of adenylate cyclase. In doses that caused a transient, 2-to 3-fold elevation of the cAMP level, theophylline and adrenaline elicited about 2.5-fold elevation of 2',5'-oligoadenylate synthetase (2-5A synthetase) activity. This increase could be prevented by actinomycin D. This suggests that the elevation of the enzyme activity in the cells was due to a transcription-dependent induction process. Theophylline and adrenaline treatment of the cell cultures also led to a 2-to 3-fold fall of the activity of the phosphodiesterase of 2',5'-oligoadenylate (2'-phosphodiesterase). This effect of adrenaline was prevented by propanolol but not by actinomycin D. In the case of adrenaline, the fall of 2'-phosphodiesterase activity was accompanied by at least 5-fold increase in the enzyme activity which did not occur if actinomycin D was present in the culture. Similarities and differences between these effects and those induced by interferon are discussed. It is concluded that cAMP is an important regulator of the enzyme system of the 2',5'-oligoadenylate metabolism. 2',5'-Oligoadenylate, in turn, was found to act on the activity of phosphodiesterase of cyclic AMP. The cAMP phosphodiesterase activity in the NIH 3T3 cell lysates was activated 2- to 2.5-fold at physiological concentrations (10(-9) to 10(-7) M) of both the phosphorylated form of oligoisoadenylate, ppp(5'A2'p)n5'A2'OH, and the dephosphorylated form, HO(5'A2'p)25'A2'OH. The phosphorylated form of oligoisoadenylate also activated partially purified preparations of cAMP phosphodiesterase. The data obtained in this study allow us to consider cAMP and 2',5'-oligoadenylate as the key metabolites that may be used in the cells to form a complex, interconnected, multifunctional circuit that involves the interferon enzyme system and the system of cyclic AMP metabolism and governs essential cell functions, as regulation of RNA metabolism and protein synthesis, cell growth and differentiation.

[Effect of benzimidazole derivatives and levamisole (phenylimidothiazole) on cyclic 3':5'-AMP phosphodiesterase from pig brain]. / Deistvie proizvodnykh benzimidazola i levamizola (fenilimidotiazola) na fosfodiésterazu tsiklicheskogo 3':5'-AMP iz mozga svin'i.

The effects of phenylimidothiazole and some benzimidazole derivatives on phosphodiesterase of cyclic 3':5'-AMP (cAMP) from pig brain were studied. Depending on their concentrations the compounds tested activated or inhibited the enzyme activity. A correlation between the effects of benzimidazoles and phenylimidothiazole which is known to exert an immunomodulating action was observed.

[Interaction between cyclic adenosine-3':5'-monophosphate phosphodiesterase and structural analogs of the substrate]. / Vzaimodeistvie fosfodiesterazy tsiklicheskogo adenozin-3':5'-monofosfata so strukturnymi analogami substrata.

The interaction between synthetic structural analogs of cyclic adenosine-3':5'-monophosphate (3':5'-AMP) and rat liver 3':5'-AMP phosphodiesterase was studied. Various groups, including those capable of covalent binding to the protein, were injected into certain sites of the 3':5'-AMP molecule. All the compounds tested exerted an inhibiting effect; in seven cases this effect was irreversible. Some peculiarities of 3':5'-AMP binding in the enzyme active center are discussed.