Ectonucleotidases and Epilepsy

Abstract

Adenosine has been proposed as an endogenous anticonvulsant which can play an important role in seizure ini-tiation, propagation and arrest. Extracellular ATP and adenosine are able to modulate synaptic activity through activation of P2 (P2X and P2Y) and P1 receptors (A 1 , A 2A , A 2B , and A 3), respectively. Besides the release of adenosine per se, the levels of ATP and adenosine in the synaptic cleft are controlled by a complex cascade of cell surface-localized enzymes collectively known as ectonucleotidases. These enzymes are capable of hydrolyzing nucleoside triphosphates, diphos-phates and monophosphates to their respective nucleosides. There are four major families of ectonucleotidases: ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases), ecto-nucleotide pyrophosphatase/phosphodiesterases (E-NPPs), alkaline phosphatases and ecto-5'-nucleotidase. All these members have specific physiological functions in the brain. In this review, the involvement of ectonucleotidases in the pathophysiology of brain disorders, such as seizures and epilepsy, is discussed. A brief introduction about the general characteristics of these enzymes is followed by a discussion about the role of ectonucleotidases in epilepsy and seizures and the implications for future treatments.