Effects of pentobarbital on incorporation of plasma palmitate into rat brain.
BACKGROUND
Barbiturates are reported to reduce brain oxidative metabolism and brain free fatty acid release during ischemia by mechanisms that are as yet unclear. To elucidate their action on brain lipid metabolism, an in vivo method was used to quantify the effect of pentobarbital on the incorporation of radiolabeled palmitic acid from blood into lipids of the rat brain.


METHODS
[9,10(-3)H]-Palmitate was infused intravenously in an awake rat or in a rat lightly anesthetized or made comatose by pentobarbital. Twenty minutes after infusion was begun, the rat was killed and non-3H2O radioactivity in individual brain lipid compartments was determined. Incorporation coefficients (k*) were calculated by dividing the lipid compartment radioactivities by the integrated plasma radioactivity to 20 min.


RESULTS
Net brain k* for [9,10(-3)H]-palmitate was reduced by 36-40% in pentobarbital-anesthetized rats. This reduction was unrelated to depth of anesthesia or to the presence of hypercapnia and acidosis, because breathing 7.5% CO2 had no effect on k* in awake rats. Anesthesia reduced radiolabel incorporation into phospholipids by 46-53% and into neutral lipids by 20-26% but did not change the distribution of radiolabel among phospholipid or neutral lipid classes.


CONCLUSIONS
Pentobarbital has a profound effect on brain lipid metabolism. It reduces incorporation of plasma palmitate into brain, more so into phospholipids than into neutral lipids, independently of changes in cerebral blood flow. Reduced incorporation likely reflects reduced turnover of palmitate within brain lipids (mainly phosphatidylcholine), consistent with evidence that barbiturates also reduce release of free fatty acids during brain ischemia.
Yamazaki
S
S
Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892.
DeGeorge
J J
JJ
Bell
J M
JM
Rapoport
S I
SI
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010168:Palmitates / Q000097:blood / Q000493:pharmacokinetics*; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
D010168:Palmitates; D010424:Pentobarbital