[Effects of cordarone on Ca2+-dependent cellular systems]. / Deistvie kordarona na Ca2+-zavisimye sistemy kletki.

Cordarone was studied for effects on the pharmacological receptors of myocardial potential-dependent Ca channels, on the receptor-dependent increase in platelet Ca2+ content, on muscarinic cholinergic receptors of the M1- and M2-type, and on calmodulin regulation of cAMP phosphodiesterase (PDE). Without showing selectivity, cordarone is able to interact both with M1-, and M2-muscarinic choline receptors with Ki = 5.3-5.6 microM. Cordarone was found to displace [3H]-nitrendipine with Ki = 1.25 microM and [3H]-desmethoxyverapamil with Ki = 1 microM. The pattern of ligand displacement suggests that the interaction of cordarone with these receptors has no competition. Cordarone was demonstrated to affect neither PDE activity nor its activation with calmodulin. Cordarone suppressed a platelet activation factor-induced increase in intracellular Ca2+ levels in the thrombocytes. Thus, cordarone is capable of affecting Ca2(+)-dependent processes at Ca2+ entry across the potential-dependent Ca channels and influencing the receptor-dependent platelet Ca2+ mobilization and muscarinic cholinergic regulation. The above effects may underlie antiarrhythmic action and determine vascular dilating and anti-fibrillating properties of cordarone.

[Adenylate cyclase system of synaptosomes from the rat cerebral cortex during acute stress]. / Adenilattsiklaznaia sistema sinaptosom kory golovnogo mozga krys pri ostrom stressornom vozdeistvii.

Synaptosomes and synaptic membranes were studied in brain cortex of rats after 6 hrs emotional-painful stress. No alterations were observed in beta-adrenoreceptors, adenylate and guanylate cyclases to the end of the second day after the acute stress action.

[Effect of cordarone on the cellular adrenergic systems]. / Deistvie kordarona na adrenergicheskie sistemy kletki.

Cordarone was examined for its effects on alpha- and beta-adrenergic receptors and adenylate cyclase (AC) of some tissues. Cordarone was shown to suppress the binding of [3H]-clonidine with alpha 2-receptors of the rabbit brain (Ki = 4 microM) and that of [3H]-prazosin with alpha 1-receptors of the rat liver (Ki = 22 microK), but not to displace [3H]-dihydroalprenolol from rabbit cardiac and pulmonary beta 1-receptors and from beta 2-receptors of rat reticulocytes and human lungs. Cordarone failed to affect the activity of rabbit heart and lung AC, as well as that of thrombocytes and human lungs, but showed a 80% inhibition of the activating effect of isoproterenol on reticulocyte AC. It was suggested that the effect of cordarone on reticulocytes was not mediated by beta-receptors and was tissue specific and dependent on the characteristics of AC regulation in these cells. Cordarone's antiadrenergic effect found in vitro may be one of the causes of its coronary dilating and antiarrhythmic effects.

[The beta-adrenergic receptor and adenylate cyclase of rat reticulocytes as a test system for screening pharmacologic preparations]. / Beta-adrenergicheskii retseptor i adenilattsiklaza retikulotsitov krysy kak test-sistema dlia skrininga farmakologicheskikh preparatov.

The effect of cardio- and neurotropic drugs was studied on beta 2-adrenergic receptors and coupled adenylate cyclase (AC) from rat reticulocytes. Trifluperazine, chlorpromazine, levomepromazine, metaphenazine, haloperidol, (+) and (-) isomers of butaclamol, as well as imipramine, vinblastine and verapamil, at a concentration of 10(-4) M failed to influence AC stimulation by isoproterenol. Thioproperazine and trifluperidol inhibited isoproterenol-stimulated AC with Ki = 4.0.10(-5) M and Ki = 4.5.10(-5) M, respectively. This inhibitory effect was due to the direct action of thioproperazine and trifluperidol on the beta-adrenergic receptors, since this drugs displace the receptor-bound (3H) dihydroalprenolol with Ki = 5.10(-6) M and 9.10(-6) M, respectively. The results obtained suggest that adrenolytic effect of trifluperidol and thioproperazine might play a significant role in their side effects.

[Multiple forms of cyclic nucleotide phosphotransferases in mouse thymocytes]. / Issledovanie mnozhestvennykh form fosfodiésterazy tsiklicheskikh nukleotidov v timotsitakh myshei.

The presence of cAMP- and cGMP- specific phosphodiesterases in mouse thymocytes has been demonstrated. Sucrose density gradient centrifugation revealed two peaks corresponding to cAMP-phosphodiesterase (3.6S and 6.0S) and one peak corresponding to cGMP-phosphodiesterase (6.6S). Gel filtration demonstrated high molecular forms of the enzymes; according to the rechromatography data, cAMP and cGMP phosphodiesterases are represented by oligomers containing subunits with Ms 45 000 and 160 000 respectively. Incubation of thymocyte lysates for 24-48 hours led to a decrease of the number of high molecular weight forms and an increase in the number of low molecular weight forms paralleled with a rise in V and Km values.