Adenosine-induced modulation of excitatory amino acid transport across isolated brain arterioles.
OBJECTIVE
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.
Grant
Gerald A
GA
Department of Neurological Surgery, University of Washington, Seattle, Washington 98104, USA. hrwinn@u.washington.edu
Meno
Joseph R
JR
Nguyen
Thien-Son
TS
Stanness
Kathe A
KA
Janigro
Damir
D
Winn
Richard H
RH
D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D001224:Aspartic Acid / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D002560:Cerebrovascular Circulation; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011061:Poly A / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D020030:Nitric Oxide Donors; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D009599:Nitroprusside; D011061:Poly A; D001224:Aspartic Acid; D018698:Glutamic Acid; D000241:Adenosine