Pharmacology of ectonucleotidases: Relevance for the treatment of cardiovascular disorders

ATP and other extracellular nucleotides have diverse and potent effects in different organs. Evidence indicates that extracellular nucleotides and nucleosides deliver crucial signals by acting upon a wide variety of purinergic receptors, which include 19 members separated in three families. Purinergic receptors encompass adenosine-sensitive receptors (P1) as well as the ATP and ADP-responsive receptors (P2). On the other side, P2 receptors are divided into ionotropic P2X receptors and G protein-coupled receptors P2Y. This system of purinergic signaling is made further complex by the fact that ectonucleotidases, membrane bound enzymes, participate in the metabolism of extracellular nucleotides, which are released by cells. Hence, ectonucleotidases are important modulators of purinergic receptor function. It should be pointed out that the ectonucleotidases includes enzymes with different substrate preferences and by their action generate different nucleotides and nucleosides as well as phosphate and pyrophosphate. A growing body of evidence points toward the fact that the expression pattern of different ectonucleotidases and purinergic receptors is implicated in several cardiovascular disorders. In this perspective, a short account is given on the role of ectonucleotidases into the pathobiology of some cardiovascular disorders and the need to develop a novel pharmacology based on those recent findings.