INTRAVENOUS-INJECTION OF [1-C-14] ARACHIDONATE TO EXAMINE REGIONAL BRAIN LIPID-METABOLISM IN UNANESTHETIZED RATS

INTRAVENOUS-INJECTION OF [1-C-14] ARACHIDONATE TO EXAMINE REGIONAL BRAIN LIPID-METABOLISM IN UNANESTHETIZED RATS
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DOI:
10.1002/jnr.490240311
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发表时间:
1989-11-01
影响因子:
4.2
通讯作者:
RAPOPORT, SI
RAPOPORT, SI
中科院分区:
医学3区
文献类型:
--
作者:
DEGEORGE, JJ;NORONHA, JG;RAPOPORT, SI

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我们研究了代谢处置和脑分布的不饱和脂肪酸,[1- 14 C]-花生四烯酸,5和240分钟之间的静脉推注后,在未麻醉的成年大鼠。注射的[1- 14 C]花生四烯酸从血浆中迅速清除,2分钟后剩余不到10%。总脑放射性,注射剂量的0.2%,5分钟接近最大值,15分钟达到峰值,然后缓慢下降。脑脂质中的放射性在所有时间均占总脑放射性的82%以上。在水溶性代谢产物的放射性是最大的,在5分钟(13%的总),并下降到5%,240分钟。蛋白颗粒相关的放射性逐渐上升到7%的峰值,120分钟。在脂质部分,超过92%的放射性是在甘油脂,与大于81%的磷脂。肌醇磷酸甘油酯中的放射性在5 min时达到最大值(磷脂放射性的47%);到20 min时下降至34%,而胆碱磷酸甘油酯中的放射性在15 min时达到峰值(磷脂放射性的41%),此后保持恒定。相反,在实验过程中,乙醇胺磷酸甘油酯的放射性从7%增加到17%。脑切片的定量放射自显影显示,[1- 14 C]花生四烯酸在灰质区的掺入量是在白质区的1.5- 3倍。根据从血浆中摄取脑脂肪酸的模型分析数据。[1-14]花生四烯酸酯从血浆到具有完整血脑屏障的脑区域的单向转移常数k的估计值范围为0.0005至0.0015 ml·cm-1。sec-1. cntdot. g ~(-1),并与[9,10-H]棕榈酸酯相关。结果表明,清醒动物的脑磷脂代谢,可以检查区域和定量使用静脉注射[1- 14 C]-花生四烯酸结合定量放射自显影和生化分析。
We examined the metabolic disposition and brain distribution of an unsaturated fatty acid, [1-14C]-arachidonate, between 5 and 240 min following its intravenous bolus injection in unanesthetized adult rats. Injected [1-14C]arachidonate was cleared rapidly from plasma, with less than 10% remaining by 2 min. Total brain radioactivity, 0.2% of the injected dose, was near maximal by 5 min, reached a peak by 15 min, then slowly declined. Radioactivity in brain lipids constituted greater than 82% of the total brain radioactivity at all times. Radioactivity in aqueous-soluble metabolites was greatest at 5 min (13% of total) and declined to 5% by 240 min. Protein pellet-associated radioactivity gradually rose to a peak of 7% by 120 min. Within the lipid fraction, more than 92% of radioactivity was in glycerolipids, with greater than 81% in phospholipids. Radioactivity in inositol phosphoglyceride was maximal at 5 min (47% of phospholipid radioactivity); and declined to 34% by 20 min, whereas radioactivity in choline phosphoglyceride peaked at 15 min (41% of phospholipid radioactivity) and was constant thereafter. In contrast, radioactivity in ethanolamine phosphoglycerides increased from 7 to 17% during the course of the experiment. Quantitative autoradiography of brain sections indicated incorporation of [1-14C]arachidonate into gray-matter regions was 1.5- to threefold that into white-matter regions. The data were analyzed in terms of a model for brain fatty acid uptake from plasma. Estimates of unidirectional transfer constants, k, for [1-14]arachidonate from plasma to brain regions with an intact blood-brain barrier ranged from 0.0005 to 0.0015 ml .cntdot. sec-1 .cntdot. g-1 and were correlated with those for [9,10--H]palmitate. The results indicate that brain phospholipid metabolism in awake animals can be examined regionally and quantitatively using intravenous injection of [1-14C]-arachidonate combined with quantitative autoradiography and biochemical analysis.