Alanko J, Riutta A, Mucha I, Vapaatalo H, Metsä-Ketelä T
Department of Biomedical Sciences, University of Tampere, Finland.
Free Radic Biol Med. 1993 Jan;14(1):19-25. doi: 10.1016/0891-5849(93)90505-o.
We have shown earlier that catecholamines have opposite regulative effects on prostaglandin (PG)E2 and leukotriene (LT)B4 formation with a receptor-independent mechanism in human polymorphonuclear leukocytes (PMNs) and whole blood. To shed further light on the mechanisms involved and structure-action relationship, we tested the effects of phenols (catechol, hydroquinone, phenol, and resorcinol) on the synthesis of PGE2 and LTB4 in human A23187-stimulated PMNs. To study the mechanism of how phenols influence PGE2 and LTB4 synthesis, their peroxyl radical-scavenging properties were analyzed. In general, low concentrations of phenols stimulated (catechol > hydroquinone >> phenol) and high concentrations inhibited (resorcinol > catechol > hydroquinone > phenol) PGE2 formation. Resorcinol was different from the other phenols: It did not stimulate PGE2 synthesis at all, but it was effective inhibitor at high concentrations. Phenols had only an inhibitory effect on LTB4 formation (catechol = hydroquinone >> phenol > resorcinol). The order of both stochiometric factors and reactivities of phenols for scavenging peroxyl radicals was catechol > hydroquinone > resorcinol >> phenol. According to these results, phenols having hydroxyl groups in ortho- or paraposition have the greatest stimulative effect on PGE2 synthesis, the highest inhibitory action on LTB4 synthesis, and are good antioxidants. Resorcinol, having hydroxyl groups in the metaposition, behaves differently. It neither stimulates PGE2 nor inhibits LTB4 formation, but it is the most potent inhibitor of PGE2 formation. In spite of resorcinol's two hydroxyl groups, it mimics as an antioxidant phenol more than catechol and hydroquinone.
我们之前已经表明，儿茶酚胺对人多形核白细胞（PMN）和全血中前列腺素（PG）E2和白三烯（LT）B4的形成具有相反的调节作用，其作用机制不依赖于受体。为了进一步阐明其中涉及的机制以及构效关系，我们测试了酚类物质（儿茶酚、对苯二酚、苯酚和间苯二酚）对人A23187刺激的PMN中PGE2和LTB4合成的影响。为了研究酚类物质影响PGE2和LTB4合成的机制，分析了它们清除过氧自由基的特性。一般来说，低浓度的酚类物质刺激（儿茶酚>对苯二酚>>苯酚），高浓度抑制（间苯二酚>儿茶酚>对苯二酚>苯酚）PGE2的形成。间苯二酚与其他酚类物质不同：它根本不刺激PGE2的合成，但在高浓度时是有效的抑制剂。酚类物质仅对LTB4的形成有抑制作用（儿茶酚=对苯二酚>>苯酚>间苯二酚）。酚类物质清除过氧自由基的化学计量因子和反应活性顺序为儿茶酚>对苯二酚>间苯二酚>>苯酚。根据这些结果，在邻位或对位具有羟基的酚类物质对PGE2合成具有最大的刺激作用，对LTB4合成具有最高的抑制作用，并且是良好的抗氧化剂。在间位具有羟基的间苯二酚表现不同。它既不刺激PGE2的形成，也不抑制LTB4的形成，但它是PGE2形成的最有效抑制剂。尽管间苯二酚有两个羟基，但它比儿茶酚和对苯二酚更像抗氧化酚。
