Prostaglandin uptake and metabolism by the perfused rat liver
Prostaglandin uptake and metabolism by the perfused rat liver
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灌注大鼠肝脏对前列腺素的摄取和代谢
DOI：
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发表时间：
1970
影响因子：
7.3
通讯作者：
J. Shaw
中科院分区：
文献类型：
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作者：
W. Dawson;S. Jessup;W. Mcdonald;P. Ramwell;J. Shaw
1.洋地黄素是一种C20不饱和脂肪酸，具有多种生理作用，但作用时间短。本文研究了大鼠离体肝脏灌流对循环血中前列腺素E_1（PGE_1）和前列腺素F_（1 α）的清除速度及其代谢。2将放射性标记的PGE_1或PGF_（1 α）单次注入肝动脉或门静脉，或将甘草素经肝循环2.5h，测定胆汁、血液和肝脏提取物中放射性的分布。通过比较进样碳和氚标记标准品后的放射性分布，以及薄层色谱法、气液色谱法、紫外和生物测定分析，推断代谢的放射性产物的性质。3.单次注射1- 14 C PGE_1，表明肝脏在一次传代中可有效清除循环中89-95%的PGE_1。排除胆汁排泄作为原型PGE 1消除的主要途径，因为在胆汁中仅检测到0.3 - 0.8%的注射放射性。在1- 14 C PGE 1的再循环期间，11-19%的注入放射性被检测为交换的14 CO2。通过PGE 1脱羧产生的其他片段鉴别肝脏内检测到的放射性，这些片段掺入脂肪酸，然后掺入磷脂。4使用5，6 - 3 H PGE 1进行的研究以及与使用1- 14 C PGE 1获得的结果的比较显示，排泄到胆汁中的放射性百分比增加了30倍，表明胆汁排泄可能是消除小于C20前列腺素的化合物的主要途径。通过碱处理后形成PGB化合物推断环戊烷环完整的证据; 9- 3 H PGF 1 α的胆汁排泄也相似。此外，单次注射5，6 - 3 H PGE 1后，在肝脏（37%）和血液（43%）中检测到的放射性增加具有PGE 1的溶剂分配和薄层色谱特性，但与极性小于C20母体结构的化合物相关。5这些结果表明，大鼠肝脏对循环中的甘草素的快速摄取。洋地黄素的脱羧导致药理学失活。产物排泄到胆汁和静脉流出物中。这些过程将缩短前列腺素注射后的效应持续时间。
1 The prostaglandins are C20 unsaturated fatty acids which exhibit diverse physiological effects of short duration. We have investigated the speed of removal of PGE1 and PGF1α from the circulating blood and their subsequent metabolism by the isolated perfused rat liver. 2 Following either a single injection of radiolabeled PGE1 or PGF1α into the hepatic artery or portal vein, or recirculation of prostaglandins through the liver for 2·5 h, the distribution of radioactivity within extracts of bile, blood and liver was determined. The nature of the radioactive products of metabolism was inferred by comparison of the distribution of radioactivity after injecting carbon and tritium labelled standards, and by thin‐layer chromatography, gas‐liquid chromatography, ultraviolet and bioassay analysis. 3 A single injection of 1–14C PGE1 indicated that the liver could efficiently remove 89–95% of circulating PGE1 on a single passage. Biliary excretion was excluded as a major route for elimination of unchanged PGE1, because only 0·3–0·8% of the injected radioactivity was detected in the bile. During recirculation of 1–14C PGE1, 11–19% of the injected radioactivity was detected as exchanged 14CO2. The radioactivity detected within liver was identified with further fragments resulting from decarboxylation of PGE1, which were incorporated into fatty acids and then phospholipids. 4 Studies with 5,6–3H PGE1, and comparison with the results obtained using 1–14C PGE1, revealed a 30‐fold increase in the percentage of radioactivity excreted into the bile, suggesting that biliary excretion may be a major route for elimination of compounds smaller than C20 prostaglandin. Evidence that the cyclopentane ring was intact was inferred by formation of a PGB compound on treatment with alkali; similar biliary excretion of 9–3H PGF1α also occurred. In addition, the increased radioactivity detected within the liver (37%) and blood (43%) after a single injection of 5,6–3H PGE1 had the solvent partition and thin‐layer chromatography properties of PGE1, but were associated with a less polar compound smaller than the C20 parent structure. 5 These results indicate rapid uptake of circulating prostaglandins by the rat liver. Decarboxylation of prostaglandins results in pharmacological inactivation. The products are excreted into the bile and venous effluent. These processes would curtail the duration of effects following prostaglandin injection.