The potent effects of purines were first reported in 1929. The first purinoceptors were defined in 1978 only, while arguably, they are the most abundant receptors in living organisms and appeared early in evolution. Separate membrane receptors for adenosine (P1 receptors) and ATP (P2 receptors) were recognized in 1978 and, later, P2 receptors were divided into ionotropic P2X and metabotropic P2Y receptors on the basis of mechanism of action, pharmacology and molecular cloning. P2X receptors are classical cationic ligand-operated channels that upon ATP binding open the pore permeable to Na+, K+ and Ca2+. They are trimers formed from individual subunits encoded by seven distinct genes (designated P2X1-7). Based on phylogenetic similarity, presence of amino acids important for ligand binding and selectivity of G-protein coupling, two distinct P2Y subgroups with a high level of sequence divergence are recognized: the P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11 subgroup (GPCR-A11) and the P2Y12, P2Y13, and P2Y14 subgroup (GPCR-A12). Receptors of the first subgroup principally use Gq/G11 to activate the phospholipase C/inositol triphosphate (InsP3) endoplasmic reticulum Ca2+-release pathway, whereas receptors of the second subgroup almost exclusively couple to Gi/o, which inhibits adenylyl cyclase and modulate ion channels. P2Y receptors can be stimulated by a wider range of nucleotides such as ATP, ADP, UTP, UDP and UDP-glucose.
 Purinergic signaling in the nervous system: an overview. Maria P. Abbracchio1, Geoffrey Burnstock2, , Alexei Verkhratsky3, 4, Herbert Zimmermann. Trends Neurosci. 2009, 32, 19-29.
 InternationalUnion of Pharmacology. Update and subclassification of the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. M.P. Abbracchio et al. Pharmacol. Rev. 2006, 58, 281-341.