Abstract

The mechanism for the efflux of taurocholic acid (TC) across the blood-brain barrier (BBB) was studied by examining the elimination of [³H]TC after microinjection into the cerebral cortex. The efflux of [³H]TC from the brain was saturable with a V_max of 15.0 pmol/min/g brain and aK_m value of 0.396 nmol/0.2 μl injectate. Efflux was inhibited by cholic acid (CA), a cationic cyclic octapeptide (octreotide; a somatostatin analogue) and an anionic cyclic pentapeptide (BQ-123; an endothelin receptor antagonist), with an IC₅₀ value of 1.09 nmol/0.2 μl injectate, 1.12 nmol/0.2 μl injectate and 0.12 nmol/0.2 μl injectate, respectively. Probenecid (20 nmol/0.2 μl injectate), but notp-aminohippuric acid (10 nmol/0.2 μl injectate), inhibited the brain efflux of [³H]TC. In addition, elimination of [³H]BQ-123 after microinjection was saturable with a V_max of 20.8 pmol/min/g brain and aK_m of 2.92 nmol/0.2 μl injectate; it was also inhibited by TC with an IC₅₀ value of 0.074 nmol/0.2 μl injectate. In contrast, no significant efflux of [¹⁴C]octreotide from the brain was observed until 60 min after microinjection. These results suggest that both TC and BQ-123 are transported from the brain to the circulating blood across the blood-brain barrier via specific mechanisms. Although mutual inhibition was observed between TC and BQ-123, kinetic analysis suggested that the two transport systems differ.