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Modulation of ischemia-evoked release of excitatory and inhibitory amino acids by adenosine A1 receptor agonist.

Abstract：

:Adenosine has been reported to have beneficial effects against ischemic brain damage, although the mechanisms are not fully clarified. To examine the role of adenosine on the ischemia-evoked release of neurotransmitters, we applied a highly selective agonist for adenosine A1 receptor, 2-chloro-N6-cyclopentyladenosine (CCPA), into the ischemic brain using in vivo brain dialysis, which directly delivered the agonist to the local brain area. Concentrations of extracellular amino acids (glutamate, aspartate, gamma-aminobutyric acid (GABA) and taurine) and regional blood flow in the striatum of spontaneously hypertensive rats (SHRs) were monitored during cerebral ischemia elicited by bilateral carotid artery occlusion for 40 min and recirculation. Striatal blood flow and basal levels of amino acids were not affected by direct perfusion of CCPA (10 microM or 100 microM). During ischemia, concentrations of glutamate, aspartate, GABA and taurine increased up to 37-, 30-, 96- and 31-fold, respectively, when vehicle alone was administered. Administration of CCPA did not affect the changes in regional blood flow during ischemia and reperfusion. Perfusion of CCPA (100 microM), however, significantly attenuated the ischemia-evoked release of aspartate (by 70%) and glutamate (by 73%). The ischemia-induced increase of GABA tended to be decreased by CCPA, although it was not statistically significant. In contrast, both low and high concentrations of CCPA had little effect on the release of taurine during ischemia. These results suggest that stimulation of adenosine A1 receptors selectively attenuated the ischemia-evoked release of excitatory amino acids, but not of inhibitory amino acids without affecting blood flow. This modulation of the release of amino acids by adenosine A1 receptor agonists may play a protective role against ischemic neuronal damage.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Goda H,Ooboshi H,Nakane H,Ibayashi S,Sadoshima S,Fujishima M

doi

10.1016/s0014-2999(98)00559-7

subject

Has Abstract

pub_date

1998-09-18 00:00:00

pages

149-55

issue

2-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(98)00559-7

journal_volume

357

pub_type

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Modulation of ischemia-evoked release of excitatory and inhibitory amino acids by adenosine A1 receptor agonist.