Biology of purinergic signalling: Its ancient evolutionary roots, its omnipresence and its multiple functional significance

The purinergic signalling system, which utilises ATP, related nucleotides and adenosine as transmitter molecules, appeared very early in evolution: release mechanisms and ATP-degrading enzymes are operative in bacteria, and the first specific receptors are present in single cell eukaryotic protozoa and algae. Further evolution of the purinergic signalling system resulted in the development of multiple classes of purinoceptors, several pathways for release of nucleotides and adenosine, and a system of ectonucleotidases controlling extracellular levels of purinergic transmitters. The purinergic signalling system is expressed in virtually all types of tissues and cells, where it mediates numerous physiological reactions and contributes to pathological responses in a variety of diseases. © 2014 WILEY Periodicals, Inc.