PT  - JOURNAL ARTICLE
AU  - Kitazawa, Takeo
AU  - Terasaki, Tetsuya
AU  - Suzuki, Hiroshi
AU  - Kakee, Atsuyuki
AU  - Sugiyama, Yuichi
TI  - Efflux of Taurocholic Acid Across the Blood-Brain Barrier: Interaction with Cyclic Peptides
DP  - 1998 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 890--895
VI  - 286
IP  - 2
4099  - http://jpet.aspetjournals.org/content/286/2/890.short
4100  - http://jpet.aspetjournals.org/content/286/2/890.full
SO  - J Pharmacol Exp Ther1998 Aug 01; 286
AB  - 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 Vmax of 15.0 pmol/min/g brain and aKm 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 Vmax of 20.8 pmol/min/g brain and aKm 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. The American Society for Pharmacology and Experimental Therapeutics