Synthesis of 5,8,11,14,17-eicosapentaenic acid

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.     

Effect of Dequalinium on Respiration and the Inner Membrane Permeability of Rat Liver Mitochondria

The effect of the lipophilic penetrating cation dequalinium on rat liver mitochondria was studied. It was found that dequalinium dose-dependently inhibits the respiration rate of rat liver mitochondria in ADP-stimulated (V₃) and DNP-stimulated (uncoupled) states. This can be due to the fact that dequalinium is a potent inhibitor of complex III of the mitochondrial respiratory chain. It was shown that dequalinium induces a high-amplitude swelling of rat liver mitochondria. The dequalinium-induced swelling of the organelles depends on the presence of inorganic phosphate in the incubation medium: in the absence of phosphate or in the presence of the phosphate carrier inhibitor mersalyl in the phosphate-containing medium, no swelling of the mitochondria was observed. At low concentrations of dequalinium (≤10 μM), this swelling is inhibited by cyclosporin A, an inhibitor of the mitochondrial permeability transition pore. At the same time, at high concentrations of dequalinium (>10 μM), cyclosporin A becomes ineffective. It was found that in the presence of dequalinium the rate of the H₂O₂ production increased in rat liver mitochondria. Possible mechanisms of toxic effect of dequalinium chloride are discussed.     

The role of mitochondrial palmitate/Ca<Superscript>2+</Superscript>-activated pore in palmitate-induced apoptosis

The evidence of possible involvement of the mitochondrial cyclosporin A-insensitive palmitate/Ca²⁺-activated pore in palmitate-induced apoptosis is presented. It has been established that the opening of the palmitate/Ca²⁺-activated pore results in the high-amplitude swelling of mitochondria and the release of the apoptosis-inducing factor from organelles. These processes are accompanied by a short-term slight decrease of membrane potential, which recovers in 1 min. The possible role of the palmitate/Ca²⁺-activated pore in the induction of palmitate-induced apoptosis is discussed.     

Synthesis of leukotriene A4 methyl ester via acetylene intermediates

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.     

Short and long latent effects of 15-hydroxyeicosatetraenoic acid on the extinction of the acetylcholine-induced inward current in neurons of the Helix lucorum]

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.