Bilayer properties of giant magnetic liposomes formed by cationic pyridine amphiphile and probed by active deformation under magnetic forces.

We synthesize giant magnetic liposomes by a reverse-phase evaporation method (REV) using a new self-assembling Cationic Pyridine Amphiphile (CPA) derived from 1,4-dihydropyridine as liposome-forming agent and a magnetic ferrofluid based on γ-Fe(2)O(3) nanoparticles. Having in view the potential interest of CPA in targeted transport by magnetic forces, the mechanical elastic properties of such bilayers are here directly investigated in vesicles loaded with magnetic nanoparticles. Bending elastic modulus K(b) ∼ 0.2 to 5k(B)T and pre-stress τ ∼ 3.2 to 12.10(-6) erg/cm(2) are deduced from the under-field deformations of the giant magnetic liposomes. The obtained K(b) values are discussed in terms of A. Wurgers's theory.

[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.

Effect of nooglutil on benzodiazepine withdrawal syndrome and binding of 3H-spiperone with D2 receptors in rat striatum.

A new nootropic preparation nooglutil (N-(5-oxynicotinoyl)-L-glutamic acid), a positive modulator of AMPA receptors for glutamate, administered intraperitoneally in a dose of 70 mg/kg reduced anxiety of rats in the Vogel conflict test after 24-h withdrawal from chronic diazepam treatment (4 mg/kg intraperitoneally for 45 days). Nooglutil (5 nM-750 microM) had no effect on in vitro binding of (3)H-spiperone in intact rats. Systemic administration of 50 mg/kg nooglutil in vivo increased the dissociation constant and density of D(2)receptors. Increasing the dose to 100 mg/kg abolished this effect. Our findings suggest that nooglutil produces an indirect effect on the brain dopaminergic system under normal and pathological conditions and this effect is probably mediated via the glutamatergic system.

[The effect of reaferon on the opioid systems of chronically alcoholized rats]. / Vliianie reaferon na opioidnye sistemy khronicheski alkogolizirovannykh krys.

Chronic alcoholic intoxication is followed by a fall in 3H-(D-ala-2,D-leu-5)-enkephalin affinity of mu-opioid receptors with their unchanged concentrations in the rat brain cortex, by reductions in the tissue and plasma levels of beta-endorphine and met-enkephalin. A daily administration of reaferon in a dose of 10,000 IU during two fortnights completely restored both the binding affinity of the receptors and the concentrations of the peptides tested: those of beta-endorphine in the adenohypophysis and plasma and those of metenkephalin in the adrenals and plasma.

[Opiate reception in the rat brain: the effect of chronic consumption of alcohol and reaferon]. / Opiatnaia retseptsiia v golovnom mozgu krys: Vliianie khronicheskogo potrebleniia alkogolia i reaferona.

Binding properties of opiate receptors were studied in brain tissue of alcoholized rats after administration of the interferon-derived drug reaferon using equilibrium radioreceptor assay. Chronic alcohol intoxication was accompanied by a decrease in affinity of opiate mu-receptors for ligands in the animals with alcohol intoxication and ethanol withdrawal. Alterations in parameters of delta-reception and in content of mu-receptors were not found. Daily administration of reaferon at a dose of 10(4) U within 1.5 month did not affect these impairments, observed in rats, studied in intoxication. However, the drug reduced completely the alcohol effect on receptors during the withdrawal period. Possible normalizing effects of reaferon on the state of opiate receptors are discussed.

[Modification by alpha-interferon of ethanol-induced changes in the level of opioid peptides in the rat striatum and hypophysis]. / Modifikatsiia pod vliianiem alpha-interferona vyzvannykh étanolom izmenenii soderzhaniia opioidnykh peptidov v striatume i gipofize krys.

Content of Met-enkephalin in striatum and of beta-endorphin in rat hypophysis were estimated after administration of ethanol and alpha-interferon into the animals. Ethanol decreased Met-enkephalin content in striatum and of beta-endorphin in hypophysis. Preadministration of alpha-interferon into brain ventricles before ethanol administration led to an increase in concentration of Met-enkephalin, while content of beta-endorphin was unaltered. In peripheric administration alpha-interferon normalized content of beta-endorphin in adenohypophysis but did not affect the Met-enkephalin concentration. Effects of alpha-interferon on content of Met-enkephalin and beta-endorphin, related to dissimilar organization of the opiate systems in hypophysis and striatum tissues, are discussed.

[Blood levels of opioid peptides and alpha interferon under the action of dipyridamole]. / Soderzhanie opioidnykh peptidov i al'fa-interferona v krovi pri deistvii dipiridamola.

The levels of met-enkephalin (ME), beta-endorphin (BE), and alpha-interferon (a-IFN) have been determined in the human blood 1 day after dipyridamole administration. Dipyridamole led to an increase in serum a-IFN concentration up to 3 times, and to simultaneous rise of the lymphocytes ability to produce a-IFN. The content of BE did not depend on dipyridamole treatment, but ME level achieved 110 +/- 4.8 pg/ml (compare to 79.5 +/- 7.6 pg/ml in control). Positive interrelation has been found out between individual ME concentrations and lymphocyte abilities to a-IFN production with the coefficient of correlation equal to 0.69. The effect of dipyridamole on ME level is suggested to develop via a-IFN interaction with the opioid systems.

[Specific binding of mu- and delta-ligands by opiate receptors in the rat brain in the presence of reaferon]. / Spetsificheskoe sviazyvanie mu- i delta-ligandov opiatnymi retseptorami golovnogo mozga krys v prisutstvii reaferona.

The ability of recombinant alpha 2-interferon (reaferon) to compete for opiate binding sites with mu- and delta-selective compounds was determined. Reaferon was found to inhibit the binding of 3H-D-ala2, D-leu5-enkephalin, and Ki value calculated was equal to 8.5 +/- 2.6 U.10(-3)/ml. The mu-agonists reception levels were decreased in the presence of reaferon at concentrations above 500 U/ml; the Ki values for 3H-morphine, 3H-dihydromorphine, 3H-RX 783006 were found to be 3.25 +/- 0.35, 4.28 +/- 0.81 and 6.51 +/- 1.27 U.10(-4)/ml, respectively. When reaferon was added into reaction medium at concentrations more than 5.10(3) U/ml the specific receptor binding of opiate antagonist 3H-naloxone was demonstrated to be increased and this effect was reversed with 100 mM NaCl. The existence of allosteric reaferon binding site which coupled with naloxone sensitive receptor was suggested to explain the results obtained.

[Opiate receptor binding of naloxone in the rat brain: effect of sodium ions]. / Opiatnaia retseptsiia naloksona v golovnom mozge krys: vliianie ionov natriia.

The binding levels and opiate receptor binding parameters were determined for 3H-naloxone in rat brain in the presence of NaCl added in vitro. An addition of NaCl at concentrations of 5-35 mM to the reaction medium caused an increase in the level of the antagonist receptor binding. The maximal level of 3H-naloxone reception activation was observed in the presence of 10-20 mM NaCl and was, on the average, 25%. Both the increase in the NaCl dose in vitro and its decrease caused a gradual diminution of the Na+ effect. An analysis of opiate receptor saturation with 3H-naloxone revealed that the label interacted with one type of the binding sites irrespective of NaCl concentration. The affinity of receptor binding sites for 3H-naloxone increased already at NaCl concentration of 2.5 mM. In contrast, the apparent maximal number of binding sites did not change after NaCl addition at concentrations which coincided with the intracellular Na+ level but was decreased with an increase (up to 50-100 mM) in NaCl present in the reaction mixture. The results obtained point to the existence of two different binding sites that are coupled with the 3H-naloxone reactive opiate receptor.

[Effect of diazepam on the specific binding of 3H-(D-Ala-2, D-Leu-5)-enkephalin by striatal membranes in the rat]. / Vliianie diazepama na spetsificheskoe sviazyvanie 3H-(D-Ala-2, D-Leu-5)-énkefalina membranami striatuma krys.

The effect of a single intraperitoneal administration of diazepam (relanium) (2.5 mg/kg) on specific binding of 3H-(D-Ala-2, D-Leu-5)-enkephalin (10 nM) by the rat striatum membranes was studied. The drug was shown to increase the binding activity of opioid receptors 15 minutes after the injection. At prolongation of the animal exposure by up to 45 minutes the magnitude of the activity decreases below the control level. Under in vitro conditions diazepam shows the activating effect which is similar to that ex vivo. It was found that the changes in the opioid receptor binding activity were produced by alterations of the maximal number of specific binding sites.