Studies of cerebral β-hydroxybutyrate transport by carotid injection; effects of age, diet and injectant composition

Transport of β-hydroxybutyrate at the blood-brain barrier was studied by the carotid-injection technique of Oldendorf. β-Hydroxybutyrate permeability declined sharply with age (80–300 g rats) and, in adult rats, increased 5-fold during one week on a high fat diet. Acetoacetate and lactate permeabilities showed age and diet dependences which were similar in direction whereas DMO, urea and mannitol did not show age and diet dependent permeabilities. There was no apparent increase of β-hydroxybutyrateK_m with age, so the decline of permeability was attributed to a decline of V_max. β-Hydroxybutyrate permeability was inversely related to pH of the injectant in the alkaline range but not in the acid range, suggesting that the pH dependence reflected titration of a carrier rather than titration of the permeant. Permeability was independent of Na⁺], K⁺], Cl⁻] and SO²⁻₄. Replacing a portion of the Na⁺ with ammonium enhanced β-hydroxybutyrate uptake. This effect appeared to be due to trans alkalization, and was as expected of an A⁻/H⁺-symport or A⁻/H⁺-antipoport mechanism. Pyruvate, 4-hydroxy-α-cyanocinnamate and tetracaine inhibited, but SITS, DIDS, phloretin and methyl-isobutylxanthine did not. The data are consistent with transport by an A⁻/H⁺-symporter or A⁻/OH⁻-antiporter with properties similar to those found in erythrocytes and other cells. Induction of its activity during ketosis would spare carbohydrate both by favoring ketoacid uptake and by favoring lactate output.