Showing papers by "Akira Endo published in 1981"

Thielavin A and B, new inhibitors of prostaglandin biosynthesis produced by Thielavia terricola.

Abstract: Two potent inhibitors of prostaglandin biosynthesis, thielavin A (C31H34O10) and B (C29H30O10), were isolated from cultures of Thielavia terricola. Both of these compounds were shown to be structurally related to depsides, thus consisting of three hydroxybenzoic acid groups. Concentrations required for 50% inhibition of the conversion of 14C-arachidonic acid into prostaglandins F2 alpha plus E2 by microsomes of ram seminal vesicles were 12 microM for thielavin A and 9 microM for thielavin B, respectively. Of the enzymatic steps involved in prostaglandin synthesis, thielavin A specifically inhibited the conversion of arachidonic acid into prostaglandin H2, while prostaglandin E2 synthesis from the endoperoxide was the most sensitive to thielavin B. Thromboxane A2 synthesis from prostaglandin H2 in bovine platelet microsomes were inhibited by 50% at concentrations of 150 and 350 microM of thielavin A and B, respectively. Thielavin B was significantly effective on carrageenan-induced oedema of rats when administered intravenously but on on oral administration. The anti-inflammatory activity was not detectable with thielavin A either on intravenous injection or on oral administration.

Xanthocillin x monomethyl ether, a potent inhibitor of prostaglandin biosynthesis

Abstract: Xanthocillin X monomethyl ether, known as an antiviral antibiotic, was isolated as a potent inhibitor of ichotomomyces cejpii. The compound inhibited prostaglandin synthesis from 14C-arachidonic acid in rabbit kidney microsomes by 50% at a concentration of 0.2 μM, while prostaglandin synthesis by microsomes of ram seminal vesicle was inhibited by 50% at 20 μM. The inhibition by xanthocillin X monomethyl ether was reversible. Of the enzymatic steps involved in the synthesis of prostaglandins and thromboxanes tested, conversion of arachidonic acid into prostaglandin H2 was specifically inhibited by xanthocillin X monomethyl ether. Anti-inflammatory activity of this antibiotic on carrageenan-induced oedema in the rat foot was, however, not detectable.

Inhibition of brain glutamate decarboxylase by 4,5-dihydroxyisophthalic acid and related compounds.

Abstract: Hydroxybenzoic and phthalic acids and their related compounds were tested for inhibitory activity to brain glutamate decarboxylase. Of mono-, di-, and trihydroxybenzoic acids, gallic acid was the most inhibitory, giving 50% inhibition at a concentration of 0.17 mm. Dihydroxybenzoic acids were less inhibitory than the trihydroxyacids but more than monohydroxybenzoic acids. Of the phthalic acid-related compounds tested, 4, 5-dihydroxyisophthalic acid was the most potent inhibitor, producing 50% inhibition at 0.61 μm. The inhibition of these compounds was competitive with respect to L-glutamate. The Ki values were 0.02, 1.2 and 4.9 pM for 4, 5-dihydroxyisophthalic acid, 5-hydroxyisophthalic acid and gallic acid, respectively. When administered intraventricularly to mice, 4, 5-dihydroxyisophthalic acid produced a significant decrease in the γ-aminobutyric acid content of the brain, resulting in induction of convulsions.

Regulation of Cholesterol Synthesis

Abstract: 数種の酵素反応 によ り合成 されるが(図-1),HMG(3hydroxy-3-methylglutary1)一CoAレ ダクターゼが その律 速 酵素 であるこ とは,種 々の生理条 件の変化,薬 物 ・ホ ルモ ンの投与及 び 日内周期 な どでみ られ る活 性 の 変 化 と,コ レス テロール合成 の変化 が完全 に対応 する ことか ら一般的 に支持 され ている1)・2)。 物質代謝系の律速酵素 は一般 に多様 な機構 によ り調 節 されてV・る場合が多V・。HMG-CoAレ ダクターゼ も以 下 に紹介す るよ うに,リ ン酸化一脱 リン酸化修飾,ホ ル モ ンの関与,LDLに よるフ ィー ドバ ック制御,さ らに 多価 フ ィー ドバ ック的制御 といった幾重 にも重 な った機 構 によ り調 節 されてい る。 これ らの調節 は,酵 素 を即座 に活 性化 ・不活 性化す る短期調節 と,酵 素 タ ンパ クの合 成 または分解速度 の調節 とい う,長 ・短2つ の機構 か ら 成 る。 1HMG-CoAレ ダ ク タ ーゼ の\"リ ン酸 化 一脱 リン酸 化\"に よ る調 節