Uptake and metabolism of plasma-derived erucic acid by rat brain.
We examined the ability of erucic acid (22:1n-9) to cross the blood-brain barrier (BBB) by infusing [14-14C]22:1n-9 (170 microCi/kg, iv and icv) into awake, male rats. [1-14C]arachidonic acid (20:4n-6) [intravenous (i.v.)] was the positive control. After i.v. infusion, 0.011% of the plasma [14-14C]22:1n-9 was extracted by the brain, compared with 0.055% of the plasma [1-14C]20:4n-6. The [14-14C]22:1n-9 was extensively beta-oxidized (60%), compared with 30% for [1-14C]20:4n-6. Although 20:4n-6 was targeted primarily to phospholipid pools, 22:1n-9 was targeted to cholesteryl esters, triglycerides, and phospholipids. When [14-14C]22:1n-9 was infused directly into the fourth ventricle of the brain [intracerebroventricular (i.c.v.)] for 7 days, 60% of the tracer entered the phospholipid pools, similar to the distribution observed for [1-14C]20:4n-6. This demonstrates plasticity in the ability of the brain to esterify 22:1n-9 in an exposure-dependent manner. In i.v. and i.c.v. infused rats, a significant amount of tracer found in the phospholipid pools underwent sequential rounds of chain shortening and was found as [12-14C]20:1n-9 and [10-14C]oleic acid. These results demonstrate for the first time that intact 22:1n-9 crosses the BBB, is incorporated into specific lipid pools, and is chain-shortened.
Golovko
Mikhail Y
MY
Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota, Grand Forks, ND 58202-9037, USA.
Murphy
Eric J
EJ
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000032:analysis; D004883:Erucic Acids / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D019301:Oleic Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002250:Carbon Radioisotopes; D004883:Erucic Acids; C049811:erucic acid; D016718:Arachidonic Acid; D019301:Oleic Acid