Role of Adenosine In Nmda Receptor Modulation in the Cerebral Cortex of an Anoxia-Tolerant Turtle (Chrysemys Picta Belli) Available to Purchase

Accumulation of the neuromodulator adenosine in the anoxia-tolerant turtle 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) receptors, we measured the effect of adenosine on NMDA-mediated Ca²⁺ transients in normoxic and anoxic turtle cerebrocortical sheets. Intracellular [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, ranging from 109±22 to 187±26 nmol l^-1. Throughout normoxic and 2 h anoxic protocols, and after single and multiple NMDA exposures, [ATP] did not change significantly, ranging from 16.0±1.9 to 25.3±4.9 nmol ATP mg^-1 protein. Adenosine caused a reduction in the normoxic NMDA-mediated increase in [Ca²⁺] from a control level of 287±35 to 103±22 nmol l^-1 (64 %). This effect is mediated by the A₁ receptor since 8-phenyltheophylline (a specific A₁ antagonist) effectively blocked the adenosine effect and N⁶-cyclopentyladenosine (a specific A₁ agonist) elicited a similar decrease in the NMDA-mediated response. Cortical sheets exposed to anoxia alone exhibited a 52 % decrease in the NMDA-mediated [Ca²⁺] rise, from 232±30 to 111±9 nmol l^-1. The addition of adenosine had no further effect and 8-phenyltheophylline did not antagonize the observed decrease. Therefore, the observed down-regulation of NMDA receptor activity during anoxia must involve additional, as yet unknown, mechanisms.