IS CYCLIC-AMP INVOLVED IN EXCITATORY AMINO ACID-EVOKED ADENOSINE RELEASE FROM RAT CORTICAL SLICES

Activation of both N-methyl-D-aspartate (NMDA) and non-NMDA receptors releases endogenous adenosine from superfused rat cortical slices. NMD A-evoked adenosine release is Ca2+-dependent and results from the extr acellular degradation of a released nucleotide, whereas non-NMDA recep tor activation releases adenosine per se in a Ca2+-independent manner. IBMX selectively inhibits NMDA- but not non-NMDA-evoked adenosine rel ease. Forskolin, but not 1,9-dideoxy-forskolin, produced a slight but significant increase in NMDA-evoked adenosine release, suggesting that the formation of cyclic AMP may somehow be involved. The inhibition o f NMDA-evoked adenosine release by IBMX is not accompanied by enhanced cyclic AMP recovery in superfusates, nor is release diminished when c yclic AMP transport is inhibited by probenecid, suggesting that the ad enosine is not derived from the extracellular metabolism of released c yclic AMP. It is possible that 5'AMP, derived from the intracellular c onversion of cyclic AMP by phosphodiesterase, might be released during NMDA receptor activation. However, more selective inhibitors of the s pecific phosphodiesterase isozymes known to be located in the cortex-f ailed to diminish NMDA-evoked adenosine release. Therefore, the effect s of both forskolin and IBMX on NMDA-evoked adenosine release could be nonspecific, coincidental and unrelated to their actions on cyclic AM P levels in the cortex. However, it is also possible that a novel IBMX -sensitive phosphodiesterase plays a primary role in converting cyclic AMP to 5'AMP intracellularly during NMDA receptor activation; the 5'A MP could then exit the cells and be converted to adenosine extracellul arly.