Adenosine-induced modulation of excitatory amino acid transport across isolated brain arterioles.

Journal Article (Journal Article)

OBJECT: Excitatory amino acid (EAA) uptake by neurons and glia acts synergistically with stereoselective transport across the blood-brain barrier (BBB) to maintain EAA homeostasis in the brain. The endogenous neuroprotectant adenosine counteracts many aspects of excitotoxicity by increasing cerebral blood flow and by producing pre- and postsynaptic actions on neurons. In the present study, the authors explored the effect of adenosine on EAA transport across the BBB. METHODS: The effects of adenosine on the permeability of the BBB and transport of aspartate and glutamate across the BBB were studied in a well-characterized isolated penetrating cerebral arteriole preparation suitable for simultaneous investigations of changes in diameter and permeability. At concentrations within the physiological to low pathophysiological range (10(-7)-10(-6) M), the net vectorial transport of [3H]L-glutamate or [3H]L-aspartate from blood to brain was significantly attenuated, whereas there was no effect of adenosine on paracellular BBB permeability to [14C]sucrose or [3H]D-aspartate. With higher concentrations of adenosine (10(-4) M and 10(-3) M) the net vectorial transport of [3H]L-glutamate and [3H]Laspartate returned toward baseline. At 10(-3) M, the permeability to [14C]sucrose was significantly altered, indicating a breakdown in the BBB. The effect of adenosine (10(-6) M) was blocked by theophylline, a blocker of the A1 and A2 receptors of adenosine. CONCLUSIONS: Adenosine-mediated modulation of glutamate and aspartate transport across the BBB is a novel physiological finding.

Full Text

Duke Authors

Cited Authors

  • Grant, GA; Meno, JR; Nguyen, T-S; Stanness, KA; Janigro, D; Winn, RH

Published Date

  • March 2003

Published In

Volume / Issue

  • 98 / 3

Start / End Page

  • 554 - 560

PubMed ID

  • 12650427

International Standard Serial Number (ISSN)

  • 0022-3085

Digital Object Identifier (DOI)

  • 10.3171/jns.2003.98.3.0554

Language

  • eng

Conference Location

  • United States