Efflux of taurocholic acid across the blood-brain barrier: Interaction with cyclic peptides

Takeo Kitazawa, Tetsuya Terasaki, Hiroshi Suzuki, Atsuyuki Kakee, Yuichi Sugiyama

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

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 a K(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 not p-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 a K(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.

Original languageEnglish
Pages (from-to)890-895
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume286
Issue number2
Publication statusPublished - 1998 Dec 1

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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