Transporter-mediated Prostaglandin e2 elimination across the rat blood-brain barrier and its attenuation by the activation of N-methyl-D-aspartate receptors

Shin Ichi Akanuma, Takanori Higuchi, Hideyuki Higashi, Go Ozeki, Masanori Tachikawa, Yoshiyuki Kubo, Ken Ichi Hosoya

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Prostaglandin (PG) E2 is involved in neuroinflammation and neurotoxicity, and the cerebral PGE2 concentration is increased in neurodegenerative diseases. Because the intracerebral concentration of L-glutamate (L-Glu) is reported to be also elevated in neurodegenerative diseases, it has been proposed that L-Glu affects PGE2 dynamics in the brain, and thus exacerbates neural excitotoxicity. The purpose of this study was to investigate the effect of intracerebral L-Glu on PGE2 elimination across the blood-brain barrier (BBB) in rats by using the intracerebral microinjection technique. [3H]PGE2 injected into the cerebral cortex was eliminated from the brain in rats, and the apparent brain-to-blood [3H]PGE2 efflux clearance was found to be 60.1 μL/(min·g brain). Intracerebral pre-administration of 50mM L-Glu significantly inhibited [3H]PGE2 elimination across the BBB and this L-Glu-induced inhibition was abolished by co-administration of an intracellular Ca2+ chelator. The intracellular Ca2+ concentration is reported to be increased via N-methyl-D-aspartate (NMDA)-type L-Glu receptors (NMDAR) and [3H]PGE2 elimination was attenuated by intracerebral pre-administration of a mixture of NMDA and D-serine. Moreover, the co-administration of antagonists of NMDAR with L-Glu abolished the attenuation of PGE2 elimination induced by intracerebral L-Glu administration. These results suggest that L-Glu attenuates BBB-mediated PGE2 elimination via NMDAR-mediated processes.

Original languageEnglish
Pages (from-to)387-393
Number of pages7
JournalDrug metabolism and pharmacokinetics
Volume29
Issue number5
DOIs
Publication statusPublished - 2014

Keywords

  • Blood-brain barrier
  • Calcium
  • Intracellular calcium ion
  • L-glutamate
  • N-methyl-D-aspartate receptor
  • Organic anion transporter
  • Prostaglandin e

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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