Ectonucleotidases and synaptic plasticity: Implications in physiological and pathological conditions

Abstract

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.

Inhibitory Avoidance Task Reveals Differences in Ectonucleotidase Activities between Male and Female Rats

“…ATP released at synapses can be hydrolyzed by a sophisticated pathway composed by ectoenzymes that include NTPDase1 or NTPDase3 (ecto-apyrase, ATP diphosphohydrolase, EC 3.6.1.5), which can transform ATP and ADP to AMP. ATP can also be hydrolyzed by NTPDase2 (ecto-ATPase, EC 3.6.1.3), producing ADP (29). The AMP produced by NTPDase1 or 3 is subsequently hydrolyzed to adenosine by an ecto-5 0 -nucleotidase (EC 3.1.3.5), a key enzyme in this pathway (30)(31)(32).…”

Apyrase and 5′-nucleotidase Activities in Synaptosomes from the Cerebral Cortex of Rats Experimentally Demyelinated with Ethidium Bromide and Treated with Interferon-β

“…The signaling action induced by extracellular ATP in the central nervous system (CNS) is directly correlated to ectonucleotidase enzyme activity [1,2]. ATP is hydrolyzed to adenosine by a conjugated action of two enzymes: apyrase (ATP diphosphohydrolase, NTPDase, EC 3.6.1.5) and 5¢-nucleotidase (EC 3.1.3.5) [3].…”

NTPDase and 5′-nucleotidase activities in synaptosomes of rabbits experimentally infected with BoHV-5

“…Bars represent mean SEM. * indicates a significant P<0.05 ectoenzymes are responsible for the hydrolysis of ATP to adenosine, controlling the extracellular levels of these biomolecules (Zimmermann 1996;Bonan et al 2001;Yegutkin 2008). ATP is a neurotransmitter involved in inflammatory and neurotoxic processes (Edwards et al 1992;Agresti et al 2005).…”