Stereospecific Permeability of Rat Blood-Brain Barrier to Lactic Acid

Blood and whole brain 14 C and 32 P activities were determined in hepatectomized rats one, two, five and ten minutes after intravenous (I.V.) injection of 14 C-labeled L-lactate or D-lactate and 32 P-labeled rat red blood cells. Whole brain homogenate 14 C was corrected for blood 14 C and chemically partitioned into 14 C-lactate, 14 CO 2 and other 14 C compounds. In controls, lactate was replaced with 14 C-D-glucose and 125 l-antipyrine. At one minute postinjection, whole brain 14 C expressed as percent of total injected 14 C activity and as percent of the antipyrine value were: antipyrine 1.78% (100%); D-glucose 1.45% (81%); L-lactate 0.36% (20%); and D-lactate 0.13% (7%). One minute after L-lactate injection, brain 14 C was 74% lactate, 5% CO 2 and 21% other compounds. Preloading rats with cold racemic Na-lactate reduced L-lactate uptake to 0.14% of the injectate (8% of antipyrine), and reduced D-Iactate uptake to 0.09% (= 5% of antipyrine). At two, five and ten minutes, brain contained more 14 C with larger fractions metabolized to CO 2 and other compounds from both L-lactate and D-lactate. The blood-brain barrier appears to contain a saturable lactate carrier exhibiting threefold L-stereospecificity to D-stereospecificity, but resulting in far less net transport than the comparable glucose carrier. Lactate transport may be limited by the scarcity of neutral lactic acid at normal blood pH.