Indomethacin modulates ischemia-evoked release of glutamate and adenosine from the rat cerebral cortex.
The effects of indomethacin (10 mg/kg) on the release of the transmitter amino acids, glutamate, aspartate, GABA, and of the purines, adenosine and inosine, from the cerebral cortex was studied in a four-vessel occlusion rat model of cerebral ischemia/reperfusion. In comparison with the control group, indomethacin significantly attenuated the ischemia-evoked release of glutamate and aspartate, but not of GABA. Adenosine levels in the cortical superfusates were significantly elevated following indomethacin administration. As indomethacin is a potent inhibitor of adenosine uptake, these results suggest that, by blocking adenosine uptake, indomethacin could elevate extracellular adenosine levels and depress glutamate and aspartate efflux as a consequence of the activation of adenosine A1 receptors.
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201.
J W
JW
Phillis
M
M
Smith-Barbour
L M
LM
Perkins
M H
MH
O'Regan
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism*; D016923:Cell Death; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004569:Electroencephalography; D018698:Glutamic Acid / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000241:Adenosine; D007213:Indomethacin