ROLE OF EXCITATORY AMINO-ACID RECEPTORS IN K+-EVOKED AND GLUTAMATE-EVOKED RELEASE OF ENDOGENOUS ADENOSINE FROM RAT CORTICAL SLICES

Abstract: : K+ and glutamate released endogenous adenosine from superfused slices of rat parietal cortex. The absence of Ca2+ markedly diminished K+‐ but not glutamate‐evoked adenosine release. Tetrodotoxin decreased K+‐ and glutamate‐evoked adenosine release by 40 and 20%, respectively, indicating that release was mediated in part by propagated action potentials in the slices. Inhibition of ecto‐5′‐nucleo‐tidase by α,β‐methylene ADP and GMP decreased basal release of adenosine by 40%, indicating that part of the adenosine was derived from the extracellular metabolism of released nucleotide. In contrast, inhibition of ecto‐5′‐nucle‐otidase did not affect release evoked by K+ or glutamate, suggesting that adenosine was released as such. Inhibition of glutamate uptake by dihydrokainate potentiated glutamate‐evoked release of adenosine. Glutamate‐evoked adenosine release was diminished 50 and 55% by the TV‐methyl‐D‐aspartate (NMDA) receptor antagonists, DL‐2‐amino‐5‐phosphonovaleric acid and (+)‐5‐methyl‐10,11‐dihydro‐5H‐dibenzo[a,d]cyclohepten‐5,10‐imine hydrogen maleate (MK‐801), respectively. The remaining release in the presence of MK‐801 was diminished a further 66% by the non‐NMDA receptor antagonist, 6,7‐dinitroquinoxaline‐2,3‐dione, suggesting that both NMDA and non‐NMDA receptors were involved in glutamate‐evoked adenosine release. Surprisingly, K+‐evoked adenosine release was also diminished about 30% by NMDA antagonists, suggesting that K+‐evoked adenosine release may be partly mediated indirectly through the release of an excitatory amino acid acting at NMDA receptors. Copyright © 1990, Wiley Blackwell. All rights reserved