Vesin M F
Institut d'Histologie et d'Embryologie, Faculté de Médecine, Université de Lausanne, Switzerland.
Neurochem Int. 1992 Dec;21(4):585-93. doi: 10.1016/0197-0186(92)90092-6.
In order to specify the source of locally synthesized prostaglandin (PG) E2 which is able to saturate the large class of low affinity PGE2 receptors in chick spinal cord, bioconversion of [1-14C]arachidonic acid into prostanoids was studied in homogenates of chick spinal cord and meninges first without addition of exogenous glutathione (GSH). Homogenates of spinal cord produced 14C-labeled PGE2, PGD2 and PGF2 alpha. Homogenates of meninges accumulated much larger amounts of [14C]PGE2 than spinal cord and surprisingly a 14C-labeled arachidonate metabolite referred to as compound Y. Compound Y generation, which was inhibited by indomethacin and enhanced by esculetin, was therefore mediated through the cyclooxygenase pathway. The fact that no labeled compound Y was detected in homogenates incubated with [3H]PGD2 or [3H]PGE2 indicated that compound Y was not a degradation product of PGs. Secondly, after addition of exogenous GSH, 14C-labeled compound Y was totally converted into [14C]PGE2. The compound Y which is converted into PGFs after a strong reduction with NaBH4 and into PGE2 after a mild reduction with GSH-hemin system or SnCl2 was therefore assumed to be a 15 hydroperoxy-PGE2 (15 HP-PGE2). These results suggest that PGE2 can be synthesized in meninges either by the classical isomerization of PGH2 or by isomerization of PGG2 followed by a GSH-sensitive reaction.
为了明确能够饱和鸡脊髓中一大类低亲和力前列腺素(PG)E2受体的局部合成PGE2的来源,首先在不添加外源性谷胱甘肽(GSH)的情况下,研究了鸡脊髓和脑膜匀浆中[1-14C]花生四烯酸向前列腺素的生物转化。脊髓匀浆产生了14C标记的PGE2、PGD2和PGF2α。脑膜匀浆中积累的[14C]PGE2比脊髓多得多,令人惊讶的是还有一种14C标记的花生四烯酸代谢物,称为化合物Y。因此,化合物Y的生成是通过环氧化酶途径介导的,它受到吲哚美辛的抑制,而七叶亭可增强其生成。在用[3H]PGD2或[3H]PGE2孵育的匀浆中未检测到标记的化合物Y,这一事实表明化合物Y不是PGs的降解产物。其次,添加外源性GSH后,14C标记的化合物Y完全转化为[14C]PGE2。因此,在用NaBH4强烈还原后转化为PGFs,在用GSH-血红素系统或SnCl2轻度还原后转化为PGE2的化合物Y被认为是15-氢过氧-PGE2(15 HP-PGE2)。这些结果表明,PGE2可以通过PGH2的经典异构化或PGG2的异构化后接一个GSH敏感反应在脑膜中合成。