Purinergic Signaling in Cardiovascular System: A Fertile Ground of Investigation

The purinergic signaling concept was firstly proposed by Burnstock in the early 1970s. At that time, the idea that ATP could act as a neurotransmitter besides its well established role as energy source for several metabolic processes faced intense resistance. Nowadays, the nucleotides’ signaling is widelyaccepted as a primitive and highly conserved system and distinct roles fornucleotides (e.g. ATP, ADP) and nucleosides (e.g. adenosine) as extracellular transmitters are now extensively described in a range of tissues. It is remarkable that nucleotides and nucleosides must reach the extracellular space in order to function as cellular messengers. This may either occur by cellular lysis or under mechanical stimulus (shear stress, hypoxia) as well as release from nerve terminals together with other neurotransmitters. Once they get the extracellular space, nucleotides will bind purinergic P2 receptors (P2X, ion channels exclusive responsive to ATP or P2Y, G-coupled receptors that may respond to ATP, ADP, UTP, UDP and UDP-glucose) while adenosine will be recognized by a class of purinoceptors named P1.

After passing their message inside the cell, these molecules must be metabolized to finishpurinergic signaling. The hydrolysis of nucleotides and nucleosides is guaranteed by a cascade of ectonucleotidases, which are ectoenzymes able to regulate the agonist availability as well as the purinoceptors activation.