Eicosatetraynoic acid

ESP Eosinophil stimulation promoter ESR Erythrocyte sedimentation rate e.s.r. Electron spin resonance ET, ET-1 Endothelin, -1 ETYA Eicosatetraynoic acid... 

The actions of non-steroidal anti-inflammatory drugs appear to be diverse. Phenylbutazone and sulfmpyrzone inhibited several effects of FMLP on PMNs increased adhesiveness, stimulation of the hexosemonophosphate shunt, lysosomal enzyme release, and formation of O These effects were explained by the ability of both phenylbutazone and sulfinpyrazone to inhibit binding of labelled FMLP to PMNs. Both were selective in that neither inhibited responses of PMNs to Csa and neither inhibited the stimulation of the hexose monophosphate shunt by latex or by opsonized Candida. The responses of PMNs to FMLP, including the release of O have also been inhibited by 5,8,11,14 eicosatetraynoic acid, an inhibitor of the metabolism of arachidonic acid h by indomethacin and by... 

Pathways of arachidonate metabolism in eicosanoid synthesis and their inhibitors. HPETE = Hydroperoxyeicosatetraenoic acid HETE = hydroxyeicosatetraenoic acid PG = prostaglandin PGI = prostacyclin TX = thromboxane. Conversions of arachidonic acid by various enzymes can be inhibited by analogues of the natural fatty acid, e g., the acetylenic analogue 5,8,11,14-eicosatetraynoic acid. 

In 1998, Sciuto and Stotts showed that post-treatment of guinea pigs with 5,8,11,14-eicosatetraynoic acid (ETYA) reduced pulmonary artery pressure after exposure to phosgene. ETYA is a competitive analogue of arachidonic acid and blocks the formation of arachidonic acid-derived mediators. Not all of the results of this study proved easy to interpret ETYA decreased lipid peroxidation (as measured by TBARS formation) and decreased oedema formation but increased leukotiene release. The authors account should be examined for details but the importance of possible species-specific effects is noted here. 

Sciuto AM and Stotts RR (1998). Posttreatment with eicosatetraynoic acid decreases lung edema in guinea pigs exposed to phosgene the role of leukotrienes. Exp Lung Res, 24, 273-292. 

Selective hydrogenation of isolated triple bonds in polyacetylenic compounds is possible with preference for a terminal triple bond to an internal one. Partial reduction of long-chain polyacetylenes affords all-c long-chain unsaturated acids, e.g., arachi-donic acid, is prepared by hydrogenation of 5,8,11,14-eicosatetraynoic acid over a deactivated Pd-on-CaCOj catalyst" ... 

A similar compound, 5,8,11,14-eicosatetraynoic acid, is also an inactivator of 15-lipoxygenase (Kuhn et al., 1984). In contrast to the results obtained with 14,15-DHA, no radiolabeling of the enzyme by the [/nef/i> /- C]methyl ester of the tetradehydro analog was observed. Instead, amino acid analysis of the inactive enzyme revealed the presence of 1 mol of methionine sulfoxide, suggesting that loss of activity resulted from oxidation of the active site rather than covalent modification. 

Cyclooxygenase is an enzyme complex known to catalyze the conversion of arachidonic and related polyunsaturated fatty acids into prostanoids (prostaglandins and thromboxanes). The acetylenic analog of arachidonic acid, eicosatetraynoic acid... 

However, in vivo experiments failed to duplicate this effect. One explanation could be avid incorporation of eicosatetraynoic acid into membrane phospholipids, as does arachidonic acid. Alternatively, the compound may be rapidly oxidized in vivo. 

Inhibition of cyclooxygenase by eicosatetraynoic acid occurred through a dual mechanism immediate inhibition was followed by a time-dependent inactivation of the enzyme. The latter could be blocked by a-naphthols, indicating a chain reaction involving a free radical . The second stage in cyclooxygenase inhibition by eicosatetraynoic acid is thus mechanism-based. 

There is a need for lipoxygenase inhibitors that are specific in that they do not also inhibit cyclooxygenase. Various poly-ynoic fatty acids are promising in this respect. One such study concerned 5,8,11-eicosatetraynoic acid [398] which inhibited formation of 12-HETE by intact platelets with ICjq = 2.4 X 10 M. In two other studies some very selective lipoxygenase inhibitors are described [399,400]. One of the most selective was 4,7,10,13-eicosatetraynoic acid. Stated ICjo values varied (intact platelets) from 3 X 10 M [400] to 7.8 X 10 M [399]. 

An extremely important approach to blocking all arachidonate metabolism is the use of 5,8,11,14-eicosatetraynoic acid [19], This acetylenic analogue of arachidonate was first used to inhibit cyclooxygenase in 1970 and was replaced in 1971 by the non steroidal anti-inflammatory drugs. Later it returned to favor when it was realized that tetraynoic acid blocks the lipoxygenase pathways too. Consequently eico-satetraynoic acid treatment does not involve the complications involved in the use of either eicosapentaenoic acid or other essential fatty acids. 

Eicosatetraynoic acid treatment of rats leads to the same deleterious effect on the gastro-intestinal mucosa as seen with indomethacin [20]. These effects, like the skin lesions in EFA deficiency, can be prevented by treatment with prostaglandins. The concept that prostaglandins of the E series are cytoprotective in the stomach has been suggested in several other body systems. One might also use the term cytoprotective to describe the prominent and widespread immunosuppressive effect of these types of arachidonate metabolites. 

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