Carrier-mediated blood-brain barrier transport of short-chain monocarboxylic organic acids.

OLDENDORF, WILLIAM H. Carrier-mediated blood-brain barrier transport of short-chain monocarboxylic organic acids. Am. J. Physiol. 224(6) : 1450-l 453. 1973.-The permeability of the blood-brain barrier (BBB) to 15 14C-labeled organic acids of metabolic interest was studied by injecting the test acids rapidly into the common carotid artery and decapitating the rat 15 set later. Brain uptake during the first brain circulatory passage was measured relative to tritiated water injected simultaneously as a highly diffusible internal standard. Competitive inhibition of uptake of the radiolabeled test substance was measured by including unlabeled competitive substances in the injected solution. Uptake of straight-chain saturated monocarboxylic acids increased with chain length and was virtually complete at lengths greater than that of hexanoate. Smaller acids exhibited uptakes which were saturable and, in the case of lactate, stereospecific. No measurable uptake of dior tricarboxylic acids was observed. Cross-inhibition was demonstrated between pyruvate and acetate, propionate, L-lactate, and butyrate but was not shown with octanoate and decanoate. Cross-inhibition was not demonstrated between pyruvate and L-phenylalanine, L-arginine, or D-glucose, indicating that the monocarboxylic acid carrier system demonstrated here is independent of blood-brain barrier amino acid and glucose transport systems.