Ectonucleotidases and synaptic plasticity: Implications in physiological and pathological conditions

Several studies have suggested a role of extracellular ATP in synaptic plas ticity. The signaling actions induced by extracellular ATP are directly cor related 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 con version of ATP to adenosine, an important neuromodulator. Our studies have shown that ectonucleotidase activities are modulated in physiological and p athological situations able to induce synaptic plasticity, such as memory, epilepsy and ischemia. Synaptosomal ectonucleotidase activities from hippoc ampus 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, ka inic acid, and kindling models. ATP diphosphohydrolase and 5'-nucleotidase activities from synaptosomes of hippocampus and cerebral cortex of rats sig nificantly and differently increased after induction of status epilepticus by pilocarpine, kainic acid, or kindling models. Furthermore, significant c hanges have been observed in ATP diphosphohydrolase and 5'-nucleotidase aft er ischemia and reperfusion in hippocampal synaptosomes of rats. The demons tration that ectonucleotidases presented the activities altered after a mem ory task, or the induction of animal models of epilepsy or ischemia-reperfu sion, suggests that these enzymes can act in the regulation of synaptic act ivity, controlling ATP and adenosine levels, depending on the synaptic plas ticity developed, in physiological or pathological conditions. Drug Dev. Re s. 52:57-65, 2001. (C) 2001 Wiley-Liss, Inc.