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Intravenous injection of [1‐ 14 C]arachidonate to examine regional brain lipid metabolism in unanesthetized rats
Author(s) -
DeGeorge J. J.,
Noronha J. G.,
Bell J.,
Robinson P.,
Rapoport S. I.
Publication year - 1989
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490240311
Subject(s) - phospholipid , chemistry , metabolism , fatty acid , arachidonic acid , lipid metabolism , white matter , endocrinology , medicine , biochemistry , biology , membrane , magnetic resonance imaging , radiology , enzyme
We examined the metabolic disposition and brain distribution of an unsaturated fatty acid, [1‐ 14 C]arachidonate, between 5 and 240 min following its intravenous bolus injection in unanesthetized adult rats. Injected [1‐ 14 C]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 aqueoussoluble metabolites was greatest at 5 min (13% of total) and declined to 5% by 240 min. Protein pelletassociated 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‐ 14 C]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 · sec −1 · g −1 and were correlated with those for [9,10‐ 3 H]palmitate. The results indicate that brain phospholipid metabolism in awake animals can be examined regionally and quantitatively using intravenous injection of [1‐ 14 C]arachidonate combined with quantitative autoradiography and biochemical analysis.