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

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.