In vivo approaches to quantifying and imaging brain arachidonic and docosahexaenoic acid metabolism.
A novel in vivo fatty acid method has been developed to quantify and image brain metabolism of nutritionally essential polyunsaturated fatty acids (PUFAs). In unanesthetized rodents, a radiolabeled PUFA is injected intravenously, and its rate of incorporation into brain phospholipids is determined by chemical analysis or quantitative autoradiography. Results indicate that about 5% of brain arachidonic acid (20:4 n-6) and of docosahexaenoic acid (22:6 n-3) acid are lost daily by metabolism and are replaced from dietary sources through the plasma. Calculated turnover rates of PUFAs in brain phospholipids, due to deesterification by phospholipase A(2) (PLA(2)) followed by reesterification, are very rapid, consistent with active roles of PUFAs in signal transduction and other processes. Turnover rates of arachidonate and docosahexaenoate are independent of each other and probably are regulated by independent sets of enzymes. Brain incorporation of radiolabeled arachidonate can be imaged in response to drugs that bind to receptors coupled to PLA(2) through G proteins, thus measuring PLA(2)-initiated signal transduction. The in vivo fatty method is being extended for human studies using positron emission tomography.
National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.
Stanley I
SI
Rapoport
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001345:Autoradiography; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D051546:Cyclooxygenase 2; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D015536:Down-Regulation; D004951:Esterification; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins; D010741:Phospholipases A / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011859:Radiography; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D014055:Tomography, Emission-Computed
D007527:Isoenzymes; D008565:Membrane Proteins; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A