[Chemical synthesis of cytochrome P-450-dependent metabolites of arachidonic acid]. / Khimicheskii sintez tsitokhrom-P-zavisimykh metabolitov arakhidonovoi kisloty.

Approaches to the chemical synthesis of cytochrome P-450-dependent metabolites of arachidonic acid and the biological role of novel metabolites in the arachidonic acid cascade are discussed.

[A comparison of the effects of 5-hydroxyeicosatetraenoic acid and hepoxilin A3 on the plasticity of the snail neuronal cholinoreceptors]. / Sravnenie éffektov 5-gidroksiéikozatetraenovoi kisloty i gepoksilina A3 na plastichnost' kholinoretseptorov neironov vinogradnoi ulitki.

The effects of two acyclic derivatives of arachidonic acid which are formed under the action of 5- and 12-lipoxygenases 5(S)-hydroxy-(6,8Z,11Z,14Z)-eicosatetraenoic acid (5-HETE) and (8R/S)-hydroxy-(11S,12S)-epoxy-5Z,9E,14Z-eicosatrienoi c acid (hepoxilin A3) on extinction of inward current evoked by local acetylcholine (ACh-current) application on soma of Helix lucorum RPa3 and LPa3 neurons were studied by the double-electrode voltage clamp technique. It was shown an increase in ACh-current extinction by 5-HETE. Hepoxilin A3 did not influence cholinoreceptor plasticity. The present results confirm earlier assumptions concerning the regulation of cholinoreceptor plasticity by acyclic eicosanoids which were formed from arachidonic acid under the influence of 5-lipoxygenase and the lack of 12-lipoxygenase metabolites in this regulation.

[Leukotriene receptor antagonists]. / Antagonisty retseptorov leikotrienov.

The review covers the aspects of classification, specificity and structure--biological activity relations in leukotriene receptor antagonists which blockade the action of the acyclic arachidonate metabolites. Prospects of designing new medicines based on these compounds are also discussed.

[Lipoxygenase inhibitors, eicosapolynoic acids, attenuate the short-term plasticity of the cholinoreceptors of snail neurons]. / Ingibitory lipoksigenaz, éikozaploiinovye kisloty. oslabliaiut kratkovremennuiu plastichnost' kholinoretseptorov neironov vinogradnoi ulitki.

On identified Helix neurones RPa3 and LPa3 with the use of the double-electrode voltage clamp technique on the membrane the influence was studied of three polyacetilenic analogues of natural polyenoic acids which were the inhibitors of their lipoxygenase oxidation on the dynamics of inward current extinction, caused by the repeated iontophoretic applications of acetylcholine to soma. It was found that 5, 8, 11, 14-eicosatetraynoic acid (30-60 microM) and 5, 8, 11, 14, 17-eicosapentaynoic acid (4-5 microM) decreased the amplitude of inward current caused by acetylcholine leading and weakened its extinction at the repeated applications. The third analogue -8, 11, 14-eicosatrynoic acid had no modulating influence on the value of current and on its extinction. The supposition was made that lipoxygenase metabolites of polyenoic acids regulated plasticity of Helix neurones cholinoreceptors. Considering different inhibiting by the used compounds of various lipoxygenases the most probable was participation in regulation of cholinoreceptors plasticity of those eicosanoids which were formed from arachidonic acid under the influence of 5-lipoxygenase. Regulating role of eicosanoids formed at the action of other lipoxygenases was not excluded.

[Short and long latent effects of 15-hydroxyeicosatetraenoic acid on the extinction of the acetylcholine-induced inward current in neurons of the Helix lucorum]. / Korotko- i dlinnolatentnye éffekty 15-gidroksiéikozatetraenovoi kisloty na ugashenie vyzvannogo atsetilkholinom vkhodiashchego toka neironov vinogradnoi ulitki.

The impact of a non-cyclized arachidonic acid derivative 15S-hydroxy-5Z, 8Z, 11Z, 13E-eicosatetraenoic acid (15-HETE) upon the dynamics of the inward current extinction, caused by repeated ion-tophoretic acetylcholine applications on the soma, was studied through a double electrode voltage clamp technique on the Helix lucorum identified neurons RPa3 and LPa3. The extracellular effect of 15-HETE (4-16 microM) was found to have a two phase influence on the inward current extinction, depending on the time of exposure to the compound. The short-latent effect (up to 60-80 min) displays itself as an extinction decrease, whereas the long-latent effect (after 60-80 min) - as an enhanced extinction. The effects caused by 15-HETE are irreversible. The short-latent one was probably due to the earlier described inhibition of 5- and 12-lipoxygenase enzymes by 15-HETE while the long-latent one - due to its intrinsic function.

[Lipoxins: study of various biosynthesis pathways]. / Lipoksiny. Issledovanie razlichnykh putei biosinteza.

Lipoxins A4 and B4 were obtained by using soybean lipoxygenase and blood cells as a source of enzymatic activity. The conditions facilitating lipoxin biosynthesis from arachidonic acid catalyzed by soybean 15-lipoxygenase were selected. A comparative analysis of lipoxin biosynthesis with the use of cell suspensions containing only granulocytes and of mixed suspensions (platelets + granulocytes and platelets + total fraction of blood leucocytes) was carried out.

[Directed biosynthesis of prostaglandin F2 alpha multiple labeled with tritium]. / Napravlennyi biosintez kratnomechennogo tritiem prostaglandina F2 alpha.

By selecting specific activators of PGF reductase and determining their optimal ratio, we have performed the directed biosynthesis of PGF2 alpha with a 45-50% yield. With the use of [5,6,8,9,11,12,14,15-3H8]arachidonic acid, multiple-labelled PGF2 alpha with molar radioactivity 6.1 TBe/mmol has been synthesised.

[Synthesis of 5,8,11,14,17-eicosapentaenic acid]. / Sintez 5,8,11,14,17-éikozopentainovoi kisloty.

A synthetic route to 5,8,11,14,17-eicosapentaynoic acid, an acetylenic precursor of 5Z,8Z,11Z,14Z,17Z-eicosapentaenoic acid, has been developed based on condensation of a propargyl synthon with omega-acetylenic fragments. Physico-chemical constants and spectral characteristics (IR, 1H-NMR, and mass-spectrometry) of the target and intermediate compounds are given.

[Synthesis of the leukotriene A4 methyl ester via acetylene intermediates]. / Sintez metilovogo éfira leikotriena A4 na osnove atsetilenovykh soedinenii.

The strategy of acyclic eicosanoid synthesis via polyacetylenic intermediates is examplified by the synthesis of the racemic leukotriene A4 methyl ester. Leukotriene synthons, namely, trideca-1,4,7-triyne and methyl 6-formyl-5,6-trans-epoxyhexanoate, were synthesised using propargylic alcohol (thrice) and 1-heptyne as starting materials. In the course of the synthesis all new carbon-carbon bonds were created through acetylenide anion condensations and (Z)-double bonds are introduced by triple bond hydrogenations. The strategy provides a straightforward and stereospecific synthetic pathway.

[Effect of vagotomy, alpha-tocopherol and arachidene on lipid peroxidation in various areas of the gastroduodenal zone in rats with experimental peptic ulcer]. / Vliianie vagotomii, al'fa-tokoferola i arakhidena na perekisnoe okislenie lipidov v raznykh otdelakh gastroduodenal'noi zony u krys pri éksperimental'noi iazvennoi bolezni.

Lipid peroxidation (LPO) was investigated in the mucosa of different gastroduodenal areas in rats with ulcer. The animals were subject to various types of vagotomy and given various drugs. The ulcerogenic agent--cystamine--was shown to have a different degree effect on the activation of free radical reactions, most pronounced in duodenal mucosa. Selective proximal vagotomy was most effective in decreasing LPO activity, as compared to total and partial vagotomy. The use of an antioxidant--alpha-tocopherol, particularly its combination with arachidene, a preparation of polyunsaturated fatty acids, prevented the development of duodenal ulcer in 75% of cases and markedly decreased both ascorbate- and NADP X H-dependent LPO. It is suggested that LPO is directly involved in the pathogenesis of ulcer and that factors attenuating the process of LPO may prevent ulcerogenesis.

[Synthesis of (8Z,11Z,14Z)-eicosatrien-5-ynoic (5,6-dehydroarachidonic) acid and its transformation into [5,6-3H]arachidonic acid and [5,6-3H]prostaglandins E2 and F2 alpha]. / Sintez (8Z,11Z,14Z)-éikozatrien-5-inovoi (5,6-degidroarakhidonovoikisloty i ee prevrashchenie v [5,6-3H]arakhidonovuiu kislotu, [5,6-3H]prostaglandiny E2 i F2 alpha.

8Z,11Z,14Z-Eicosatriene-5-ynoic acid and its tritium-labelled analogue, [5,6-3H]arachidonic acid, have been synthesized on the basis of acetylenic compounds. [5,6-3H]Arachidonic acid has been used as substrate for the enzymatic synthesis of [5,6-3H]PGE2 and [5,6-3H]PGF2 alpha.

[Synthesis of leukotriene A4 methyl ester via acetylene intermediates]. / Sintez metilovogo éfira leikotriena A4 na osnove atsetilenovykh soedinenii.

Rac-leukotriene A4 methyl ester has been synthesized from propargylic alcohol and 1-heptyne. The synthetic strategy involves the assembly of carbon chain by acetylenide anion condensations and the introduction of (Z)-double bonds by the triple bond hydrogenation.

[Isolation and characteristics of immobilized preparations of prostaglandin synthetase]. / Poluchenie i kharakteristika immobilizovannykh preparatov prostaglandinsintetazy.

Enzymatic preparations of prostaglandin synthetase were immobilized by various methods, i.e., covalent binding to the carrier, incorporation into the matrix of polyacrylamide gel and adsorption on ion-exchangers. The most representative results were obtained with the use of the absorption technique. In this case, the enzyme activity either decreased very insignificantly or remained unaffected. The stability of immobilized enzyme preparations was studied. Some kinetic characteristics of immobilized prostaglandin synthetase were obtained.