ROLE OF ADENOSINE IN NMDA RECEPTOR MODULATION IN THE CEREBRAL-CORTEX OF AN ANOXIA-TOLERANT TURTLE (CHRYSEMYS-PICTA BELLI)

Accumulation of the neuromodulator adenosine in the anoxia-tolerant tu rtle brain may play a key role in a protective decrease in excitatory neurotransmission during anoxia, Since excitatory neurotransmission is mediated largely by Ca2+ entry through N-methyl-D-aspartate (NMDA) re ceptors, we measured the effect of adenosine on NMDA-mediated Ca2+ tra nsients in normoxic and anoxic turtle cerebrocortical sheets, Intracel lular [Ca2+] was measured fluorometrically with the Ca2+-sensitive dye Fura-2. Baseline intracellular [Ca2+] and [ATP] were also measured to assess cortical sheet viability and potential toxic effects of NMDA, Baseline [Ca2+] did not change significantly under any condition, rang ing from 109+/-22 to 187+/-26 nmoll(-1). Throughout normoxic and 2 h a noxic protocols, and after single and multiple NMDA exposures, [ATP] d id not change significantly, ranging from 16.0+/-1.9 to 25.3+/-4.9 nmo l ATP mg(-1) protein, Adenosine caused a reduction in the normoxic NMD A-mediated increase in [Ca2+] from a control level of 287+/-35 to 103/-22 nmoll(-1) (64%), This effect is mediated by the Al receptor since 8-phenyltheophylline (a specific Al antagonist) effectively blocked t he adenosine effect and N-6-cyclopentyladenosine (a specific Al agonis t) elicited a similar decrease in the NMDA-mediated response, Cortical sheets exposed to anoxia alone exhibited a 52% decrease in the NMDA-m ediated [Ca2+] rise, from 232+/-30 to 111+/-9 nmoll(-1). The addition of adenosine had no no further effect and 8-phenytheophylline did not antagonize the observed decrease. Therefore, the observed down-regulat ion of NMDA receptor activity during anoxia must involve additional, a s yet unknown, mechanisms.