[Features of expression and functional activity of P2X7 receptors in bone marrow cells under the action of doxorubicin].

Mechanisms of the myelotoxic action of doxorubicin associated with changes in the expression and functional activity of P2X7 receptors have been assessed. The acute and subacute exposure of bone marrow cells to doxorubicin in vivo changed the expression of P2X7, altered the intracellular and extracellular ATP concentrations, and modulated the process of programmed cell death. These changes were associated with transformed susceptibility of hemopoietic cells to the apoptogenic action of ATP. Various possible mechanisms of realization of the apoptogenic action of ATP during acute and subacute exposure to doxorubicin are discussed.

[Radioprotective effect of hydroxy phenylethanolamine phenolic hydroxyl esters]. / Radiozashchitnyi éffekt slozhnykh éfirov po fenol'nym gidroksilam oksifenilétanolaminov.

Experiments are carried out on 3000 mice, irradiated in dose 8 Gy (LD97/30). A number of phenolic hydroxyl esters of phenylephrine, norphenylephrine and epinephrine has the high RPE (70-100%) within 1 h before irradiation. 3-esters of 3-hydroxy phenylethanolamines are active in small doses (19-50 mumol/kg) and protect per os too. RPE of 3-benzoylphenylephrine realizes via alpha 1-adrenoreceptors.

[Radiation protective effect of beta-ketoanalogs of hydroxyphenyl ethanolamines]. / Radiozashchitnyi éffekt beta-ketoanalogov oksifenilétanolaminov.

Experiments are carried out on 3400 mice, irradiated in dose 8 Gy (LD97/30). beta-Ketoanalogs of adrenaline (adrenalone, 50-150 mumol/kg), m,p-dipivaloyladrenaline (20 mumol/kg) and phenylephrine (but at 2070 mumol/kg) have the high radioprotective effect (survival is 60-100%), beta-ketoanalogs of isoprenaline and m-benzoylphenylephrine have the middle RPE (50-60%). Their effective doses (except dipivaloyladrenalone) are considerably bigger (in 9-76 times), than beta-hydroxysubstances doses, but the toxicity of benzoylphenylephrone, dipivaloyladrenalone and especially adrenalone is by far lower (consequently in 3, 8, 2, 7 and 136 times). Therapeutic indexes of beta-ketosubstances achieve 35-100.

[Effect of slow action calcium channel inhibitors on the radioprotective effect of mezaton ]. / Vliianie ingibitorov medlennykh kaltsievykh kanalov na radiozashchitnyi éffect mezatona.

Verapamil and cinnarizine decrease radioprotective effect of phenylephrine, but nifedipin (more specific inhibitor of slow calcium channel) doesn't change it. Consequently, protective effect of phenylephrine isn't realized by influx of Ca2+ ions through slow calcium channel.

[Radioprotective effect of alpha 2- adrenoreceptor agonists]. / Radiozashchitnyi éffect agonistov alfa 2- adrenotseptorov.

It is confirmed in experiments with selective antagonists, that radioprotective effects (RPE) of phenylephrine is realised by means of alpha 1--and RPE of clonidine--by means of alpha 2-adrenoceptors (AR). Guanobenz, more selective alpha 2-agonist with another structure, has high RPE too. Chemical analogues of clonidine (alpha-antagonist phentolamine, L-DOPA, DOP-serine), which don't cause selective stimulation of alpha 2-AR, don't protect mice. alpha 2-Agonists are new effective group of radioprotectors.

[The radioprotective effect of GABA-tropic substances, gamma-hydroxybutyrate and piracetam]. / Issledovanie radiozashchitnogo éffekta GAMK-tropnykh veshchestv, gamma-gidroksibutirata i piratsetama.

From experiments in mice, it is shown that with a radiation dose of 8 Gy (LD96) the radioprotective effect was exerted by gamma-aminobutyric acid (GABA), substances that increase its concentration in tissues (progabide and valproate), and synthetic agonists of both receptor types, particularly baclofen, a GABA-receptor agonist. The radioprotective effect is also exerted by gamma-hydroxybutyrate, not piracetam.

[An increase in the radioprotective effect of O-methyltyramine and mezaton by monoamine oxidase inhibitors]. / Uvelichenie ingibitorami monoaminoksidazy radiozashchitnogo éffekta O-metiltiramina i mezatona.

Specific 2-propynylamine inhibitors of monoamine oxidase (MAO) pargyline and especially chlorgyline, a selective inhibitor of MAO A (but not deprenyl, a selective inhibitor of MAO B) increase the radioprotective effect of small doses of O-methyltyramine and phenylephrine and do not change the efficacy of large doses. This is consistent with the receptor theory of the mechanism of protective action of amines.

[Significance of ED50 and therapeutic indexes of various radiation-protective agent groups]. / Znacheniia ED50 i terapevticheskie indeksy razlichnykh grupp radioprotektorov.

Radioprotective agents are divided in 3 groups: (1) cystamine, AET, cystaphos, gammaphos, and thiogammaphos with ED50 (the dose that gives a half of the maximal protective effect) of 10(3)-10(1.6) mumol/kg and therapeutic index K = LD50/ED50 = 10(0)-10(1.6); (2) 5-methoxytryptamine, phenylephrine, serotonin, and norepinephrine with ED50 = 10(1)-10(0) mumol/kg and K = 10(1.8)-10(2,6); (3) clonidine and isoprenaline with ED50 = 10(-0.5)-10(-0.8) mumol/kg and K = 10(3)-10(4). Possible causes of these differences and advantages of low ED50 and high K are discussed.

[The antihypoxic and radioprotective properties of selective adenosine receptor agonists]. / Protivogipoksicheskie i radioprotektornye svoistva selektivnykh agonistov adenozinovykh retseptorov.

The selective A1- and A2-receptor agonists L-PIA (ED50 = 0.55-0.78 mmole/kg) and NEGA (D50 = 0.05-0.1 mmole/kg) possess high antihypoxic and radioprotective effects. A2-subtype receptors may be involved in the antihypoxic and radioprotective effects of adenosine analogs.

[Radioprotective effect of nucleosides and nucleotides and the mechanism of action of adenosine]. / Issledovanie radiozashchitnogo éffekta razlichnykh nukleozidov i nukleotidov i mekhanizma deistviia adenozina.

Adenosine and a majority of adenine mononucleotides have a radioprotective action; adenine and 2'-deoxyadenosine have no radioprotective effect, and that of 3',5'-cAMP only approaches the detectable level. Ribo- and deoxyribonucleosides and nucleotides of guanine, uracil, thymine, and cytosine have no protective action. Dipyridamole increases and alkylxanthines block the radioprotective effect of adenosine. So it follows that the radioprotective effect is realized via A-receptors of the plasmatic membrane external surface.

[Mechanism of the radioprotective effect of catecholamine receptor agonists. Inclusion in the radioprotective effect of both subtypes of alpha-adrenoreceptors]. / Issledovanie mekhanizmov radiozashchitnogo éffekta agonistov katekholaminovykh retseptorov. Vkliuchenie v radiozashchitnyi éffekt oboikh podtipov al'fa-adrenoretseptorov.

alpha-Adrenoceptor agonists of both main groups, i. e. arylalkylamines and imidazolines, have a pronounced radioprotective effect. Their chemical analogs, which fail to stimulate alpha-adrenoceptors, do not protect mice. The effect of phenylephrine, adrenaline, and noradrenaline comes into play via alpha 1-adrenoceptors and that of clonidine, via alpha 2-adrenoceptors and also via alpha 1-adrenoceptors. Adrenoceptor agonists can probably manifest their radioprotective action via both subtypes of alpha-adrenoceptors. Possible intracellular mechanisms of the radioprotective action are discussed.

[Mechanism of the radioprotective effect of catecholamine receptor agonists. Inclusion in the radioprotective effect of different subtypes of beta-adrenoreceptors]. / Issledovanie mekhanizma radiozashchitnogo éffekta agonistov katekholaminovykh retseptorov. Vkliuchenie v radiozashchitnyi éffekt raznykh podtipov beta-adrenoretseptorov.

Isoproterenol of ED50 = 0.16 mumol/kg is highly effective in protecting mice against ionizing radiation and has the high therapeutical index. There are three new indications that isoproterenol exerts its radioprotective action via beta-adrenoceptors. They are: the effect of isoproterenol is prevented by three additional beta-adrenoceptor antagonists, the isoproterenol effect is reproduced by the seven studied beta-adrenoceptor agonists of different chemical structure, and with chemical analogs which fail to stimulate beta-adrenoceptors the radioprotective effect is absent. Both beta 1 and beta 2 adrenoceptor agonists are protective agents. Mechanisms of the radioprotective action are discussed.