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培养的兔肾积水皮质间质细胞的类花生酸合成

Eicosanoid synthesis by rabbit hydronephrotic cortical interstitial cells in culture.

作者信息

Danon A, Zenser T V, Thomasson D L, Palmier M O, Davis B B

出版信息

J Pharmacol Exp Ther. 1986 Jul;238(1):95-9.

PMID:3088262
Abstract

Rabbit hydronephrotic cortical interstitial cells in primary culture were labeled with [1-14C]arachidonic acid and the eicosanoids released after stimulation with bradykinin or A23187 were studied by reverse-phase high performance liquid chromatography. The major arachidonic acid metabolite formed was prostaglandin (PG)E2, comprising more than 30% of the total radioactivity released. 12-Hydroxyheptadecatrienoic acid, probably representing spontaneous breakdown of the cyclic endoperoxides PGG2 and/or PGH2, made up 10 to 15% of the radioactivity released. Other cyclooxygenase products that were released included PGF2 alpha, PGD2, 6-keto PGF1 alpha and only minute amounts of thromboxane B2. Small quantities of the lipoxygenase products 15-, 12- and 5-hydroxyeicosatetraenoic acids (HETEs) as well as leukotrienes (LT)B4, LTC4 and LTD4 were also identified. Significantly larger quantities of 15- and 5-HETEs were recovered at 2 to 5 min than after longer incubations with A23187, suggesting esterification of these HETEs into cellular phospholipids. The data indicate that interstitial cells of the hydronephrotic kidney synthesize a variety of cyclooxygenase and lipoxygenase products of arachidonic acid, which may contribute to the pathophysiology of hydronephrosis. Moreover, it is suggested that PGG2 and/or PGH2 that are released from these cells may be metabolized further by adjacent kidney cells or circulating blood elements to other eicosanoid products, thus increasing the diversity of eicosanoids synthesized in the hydronephrotic kidney.

摘要

将原代培养的兔肾积水皮质间质细胞用[1-14C]花生四烯酸标记,并用反相高效液相色谱法研究缓激肽或A23187刺激后释放的类花生酸。形成的主要花生四烯酸代谢产物是前列腺素(PG)E2,占释放的总放射性的30%以上。12-羟基十七碳三烯酸可能代表环内过氧化物PGG2和/或PGH2的自发分解,占释放放射性的10%至15%。释放的其他环氧化酶产物包括PGF2α、PGD2、6-酮PGF1α和仅微量的血栓素B2。还鉴定出少量脂氧合酶产物15-、12-和5-羟基二十碳四烯酸(HETEs)以及白三烯(LT)B4、LTC4和LTD4。与用A23187孵育较长时间后相比,在2至5分钟时回收的15-和5-HETEs量明显更大,表明这些HETEs酯化为细胞磷脂。数据表明,肾积水肾脏的间质细胞合成多种花生四烯酸的环氧化酶和脂氧合酶产物,这可能有助于肾积水的病理生理学。此外,有人提出,从这些细胞释放的PGG2和/或PGH2可能被相邻的肾细胞或循环血液成分进一步代谢为其他类花生酸产物,从而增加肾积水肾脏中合成的类花生酸的多样性。

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