Sensitivity to selective adenosine A1 and A2A receptor antagonists of the release of glutamate induced by ischemia in rat cerebrocortical slices.

Abstract

Adenosine released during cerebral ischemia is considered to act as a neuroprotectant, possibly through the inhibition of glutamate release. The involvement of A(1) and A(2A) receptors in the control of the rise of extracellular glutamate during ischemia was investigated by monitoring the effects of selective A(1) and A(2A) receptor antagonists on ischemia-evoked glutamate release in rat cerebrocortical slices.Slices were superfused with oxygen- and glucose-deprived medium and [(3)H]D-aspartate or endogenous glutamate was measured in the superfusate fractions. Withdrawal of Ca(2+) ions or addition of tetrodotoxin more than halved the ischemia-evoked efflux of [(3)H]D-aspartate or glutamate, compatible with a vesicular-like release. The glutamate transporter inhibitor DL-TBOA prevented the ischemia-evoked efflux of [(3)H]D-aspartate by about 40%, indicating a carrier-mediated efflux. The ischemia-evoked efflux of [(3)H]D-aspartate or glutamate was increased by the A(1) receptor antagonist DPCPX. The A(2A) antagonist SCH 58261 decreased [(3)H]D-aspartate or endogenous glutamate efflux (50 and 55% maximal inhibitions; EC(50): 14.9 and 7.6 nM, respectively); the drug was effective also if added during ischemia. No effect of either the A(1) or the A(2A) receptor antagonist was found on the ischemia-evoked efflux of [(3)H]D-aspartate in Ca(2+)-free medium. Our data suggest that adenosine released during cerebral ischemia can activate inhibitory A(1) and stimulatory A(2A) receptors that down- or up-regulate the vesicular-like component of glutamate release.

• Authors: Manuela Marcoli, Luca Raiteri, Andrea Bonfanti, Angela Monopoli, Ennio Ongini, Maurizio Raiteri, Guido Maura
• Journal: Neuropharmacology (Neuropharmacology) Vol. 45 Issue 2 Pg. 201-10 (Aug 2003) ISSN: 0028-3908 [Print] England
• PMID: 12842126 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Purinergic P1 Receptor Antagonists
• Receptor, Adenosine A2A
• Receptors, Purinergic P1
• Glutamic Acid

Topics

• Animals
• Brain Ischemia (metabolism)
• Cerebral Cortex (metabolism)
• Dose-Response Relationship, Drug
• Glutamic Acid (metabolism)
• In Vitro Techniques
• Male
• Purinergic P1 Receptor Antagonists
• Rats
• Rats, Sprague-Dawley
• Receptor, Adenosine A2A
• Receptors, Purinergic P1 (metabolism)