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Sensitivity to selective adenosine A1 and A2A receptor antagonists of the release of glutamate induced by ischemia in rat cerebrocortical slices
- Source :
-
Neuropharmacology . Aug2003, Vol. 45 Issue 2, p201. 10p. - Publication Year :
- 2003
-
Abstract
- Adenosine released during cerebral ischemia is considered to act as a neuroprotectant, possibly through the inhibition of glutamate release. The involvement of A1 and A2A receptors in the control of the rise of extracellular glutamate during ischemia was investigated by monitoring the effects of selective A1 and A2A receptor antagonists on ischemia-evoked glutamate release in rat cerebrocortical slices.Slices were superfused with oxygen- and glucose-deprived medium and [3H]d-aspartate or endogenous glutamate was measured in the superfusate fractions. Withdrawal of Ca2+ ions or addition of tetrodotoxin more than halved the ischemia-evoked efflux of [3H]d-aspartate or glutamate, compatible with a vesicular-like release. The glutamate transporter inhibitor dl-TBOA prevented the ischemia-evoked efflux of [3H]d-aspartate by about 40%, indicating a carrier-mediated efflux. The ischemia-evoked efflux of [3H]d-aspartate or glutamate was increased by the A1 receptor antagonist DPCPX. The A2A antagonist SCH 58261 decreased [3H]d-aspartate or endogenous glutamate efflux (50 and 55% maximal inhibitions; EC50: 14.9 and 7.6 nM, respectively); the drug was effective also if added during ischemia. No effect of either the A1 or the A2A receptor antagonist was found on the ischemia-evoked efflux of [3H]d-aspartate in Ca2+-free medium. Our data suggest that adenosine released during cerebral ischemia can activate inhibitory A1 and stimulatory A2A receptors that down- or up-regulate the vesicular-like component of glutamate release. [Copyright &y& Elsevier]
- Subjects :
- *ADENOSINES
*CEREBRAL ischemia
Subjects
Details
- Language :
- English
- ISSN :
- 00283908
- Volume :
- 45
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 10117672
- Full Text :
- https://doi.org/10.1016/S0028-3908(03)00156-4