Ectonucleotidases and synaptic plasticity: Implications in physiological and pathological conditions

Several studies have suggested a role of extracellular ATP in synaptic plasticity. The signaling actions induced by extracellular ATP are directly correlated to the activity of a group of ectonucleotidases, which includes an ecto-ATPase (EC 3.6.1.3), an ATP diphosphohydrolase (apyrase, EC 3.6.1.5), and a 5'-nucleotidase (EC 3.1.3.5). These ectoenzymes trigger enzymatic conversion of ATP to adenosine, an important neuromodulator. Our studies have shown that ectonucleotidase activities are modulated in physiological and pathological situations able to induce synaptic plasticity, such as memory, epilepsy and ischemia. Synaptosomal ectonucleotidase activities from hippocampus and entorhinal cortex were inhibited after the training session in a step-down inhibitory avoidance task in rats. Considering that adenosine has anticonvulsant effects, ectonucleotidase activities were determined after the induction of epilepsy by several animal models, such as pilocarpine, kainic acid, and kindling models. ATP diphosphohydrolase and 5'-nucleotidase activities from synaptosomes of hippocampus and cerebral cortex of rats significantly and differently increased after induction of status epilepticus by pilocarpine, kainic acid, or kindling models. Furthermore, significant changes have been observed in ATP diphosphohydrolase and 5'-nucleotidase after ischemia and reperfusion in hippocampal synaptosomes of rats. The demonstration that ectonucleotidases presented the activities altered after a memory task, or the induction of animal models of epilepsy or ischemia-reperfusion, suggests that these enzymes can act in the regulation of synaptic activity, controlling ATP and adenosine levels, depending on the synaptic plasticity developed, in physiological or pathological conditions. Drug Dev. Res. 52:57-65, 2001. (C) 2001 Wiley-Liss, Inc.