[Effect of a cholecystokinin tetrapeptide analogue on opioid reception under acute and chronic morphine administration].

Effects of a modified CCK-4, a tetrapeptide fragment of cholecystokinin, on opioid reception and cAMP level were studied. The modified CCK-4 changed the ligand binding of the opioid receptors of mu- and sigma-types in vitro. In vivo, it prevented changes in opioid reception caused by a single morphine injection or by morphine withdrawal after its long-term introduction. The CCK-4 analogue did not exert any effect in the state of intoxication after a long-term introduction of morphine or even promoted the morphine effect. The introduction of the CCK-4 analogue alone or together with morphine changed the forskoline-stimulated level of cAMP. These changes depended on the brain structure and the duration of the introduction of morphine and the CCK-4 analogue. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2006, vol. 32, no. 3; see also http://www.maik.ru.

[Biological activity of cholecystokinin-(30-33) tetrapeptide analogs].

Analogues of the endogenous peptide corresponding to the 30-33 sequence of cholecystokinin (Trp-Met-Asp-Phe-NH2) were synthesized, and their biological activity was studied. It was shown that, in rats, the N-succinylated Nle2 analogue of this tetrapeptide exhibits increased anxiolytic properties in the dark-bright chamber test and an enhanced alcohol intake by both the control animals and the long-time alcohol-dependent animals under the conditions of free choice. Introduction of an isopropyl residue into the C-terminal amide of the Nle2 analogue resulted in the appearance of anxiolytic and antialcohol activity and the ability to increase the morphine analgesic effect in the tail-flick test on rats. The two synthesized analogues retained an affinity to cholecystokinin receptors.

[Involvement of the neuropeptide cholecystokinin in the mechanisms of regulation of emotions and craving]. / Uchastie neiropeptida kholetsistokinina v mekhanizmakh reguliatsii émotsii i vlechenii.

The paper presents an idea on the organization and functions of the cholecystokinin (CCK) system. Particular emphasis is laid on the modulating influence of CCK on dopamine neuromediation in the mesolymbic structures of the brain, which are linked with the regulation of emotions and craving. Experimental and clinical studies have indicated that CCK and its preparations arrest the major manifestation of the withdrawal syndrome, including pathological craving for alcohol, and anxiety. In the post-withdrawal period, these drugs also effectively suppress alcohol craving. The designed new tetrapeptide, a CCK analogue, selectively inhibits anxiety in animals with this emotional disorder, which is followed by normalization of dopamine exchange and GABA-system functions. It is concluded that by interacting with the dopamine-system, CCK takes a direct part in the regulation of emotions and craving.

[Study of low density lipoproteins in hyperlipoproteinemia by the method of double immunodiffusion]. / Issledovanie lipoproteidov nizkoi plotnosti pri giperlipoproteidemii metodom dvoinoi immunodiffuzii.

By way of gel double immunodiffusion a certain heterogeneity of low density lipoproteins was observed to manifest itself in an additional band of immunoprecipitation. The incidence of this additional band does not exceed 1/3 of the cases of low density lipoproteins studies in normal individuals, while in those with ischaemic heart disease the additional band is found twice-thrice as often, the highest incidence being noted in patients with ischaemic heart disease and Type IIb hyperlipoproteinemia (93% of cases). The revealed immunochemical heterogeneity of low density lipoproteins was shown to be not connected with the appearance of any new, additional antigen in their structure. Most probably it is attributable to the presence of lipoprotein particles with a quantitatively different protein and lipid composition, probably of intermediate lipoprotein metabolites in blood plasma, or conformation changes in the structure of low density lipoproteins.

[The evaluation of the effect of zinc sulfate on primary immune response indices under alcoholic intoxication]. / Otsenka vliianiia sul'fata tsinka na pokazateli pervichnogo immunnogo otveta v usloviiakh alkogol'noi intoksikatsii.

Introduction of zinc sulfate in the composition of drinking liquid on the background of alcohol intoxication of animals increases the intensity of primary immune response to the sheep erythrocytes (ShE). This effect is manifested through an increase in the number of phagocytosing lymphocytes in peripheral blood, antibody forming cells in the spleen, antibody titer to ShE, and in an increase in the rosette-forming ability of lymphocytes. The data obtained indicate to the potential use of the zinc salts for immunity correction in conditions of chronic alcohol intoxication.

[Effect of alcohol intoxication on activity of enzymes in ethanol oxidation and on arginase activity in rat liver]. / Vliianie alkogol'noi intoksikatsii na aktivnost' fermentov okisleniia étanola i arginazy pecheni krys.

In chronic alcohol intoxication activity of alcohol-oxidizing systems in liver tissue was not distinctly altered as shown by estimation of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (AcDH) activities, whereas the arginase activity was increased 1.5-2-fold. At the same time, the activities ADH, AcDH and arginase tended to decrease in acute alcohol intoxication of slight and middle degree. These alterations in the enzymatic activity were more pronounced in acute intoxication occurring simultaneously with chronic alcoholization. Lethal doses of alcohol caused a decrease in ADH and AcDH activities but did not affect the arginase activity.

[Comparative evaluation of the effect of carbidine and levamisole on the E-rosette-forming activity of the lymphocytes in alcoholic intoxication]. / Sravnitel'naia otsenka vliianiia karbidina i levamizola na E-rozetkoobrazuiushchuiu aktivnost' limfotsitov pri alkogol'noi intoksikatsii.

The E-rosette formation activity of lymphocytes in human alcoholics treated with carbidine was studied. In experimental alcohol intoxication in animals the effect of carbidine on the E-rosette formation was compared with that of levamisole. The effects of the both drugs in the in vitro experiments were studied as well. The use of carbidine for treating alcoholism was shown to produce changes in the E-rosette formation indicating possible immunodulating properties of the drug. In experimental conditions of the immune response to ram erythrocytes during alcoholic intoxication the inhibitory effect of carbidine on the E-rosette formation was more pronounced. In the in vitro conditions carbidine changes the E-rosette formation in alcoholics similarly to levamisole suggesting the immunomodulating properties of carbidine.

[Effects of morphine on adenylate cyclase activity in lymphocytes of healthy subjects and patients with alcoholism and opiate addiction]. / Vliianie morfina na aktivnost' adenilattsiklazy limfotsitov zdorovykh, bol'nykh alkogolizmom i opiinoi narkomaniei.

The morphine dose 10(-7) M had practically no effect on adenylate cyclase (AC) activity in lymphocytes of healthy controls (n = 20). The same dose of morphine had a pronounced stimulating effect on the AC activity in lymphocytes of alcoholics in withdrawal (n = 16). In the group of opiate addicts in withdrawal (n = 9) morphine had also a stimulating effect, which differed significantly from controls (33.7 +/- 13.8; P. 0.02). The range of fluctuation of morphine influence on AC activity during the first week of hospitalization was 162.9 +/- 33.0% in alcoholics and 30.4 +/- 4.6% in opiate addicts (P 0.01).

[Effect of carbidine on parameters of ethanol oxidation in experimental alcoholic intoxication]. / O vliianii karbidina na pokazateli okisleniia étanola pri éksperimental'noi alkogol'noi intoksikatsii.

The effect of carbidine on enzymes of ethanol and acetaldehyde oxidation, the rate of ethanol elimination and the parameters of ethanol consumption were studied during long-term alcoholic intoxication. Carbidine administration was shown to increase the activity of alcohol dehydrogenase of the liver tissue, to decrease the activity of aldehyde dehydrogenase with a low Km to acetaldehyde. Also, the rate of ethanol elimination and a relative amount of consumed ethanol increase at the expense of an increase of the volume of consumed liquid.