Purinergic receptors are nucleoside receptors, adenosine receptors (A1, A2_{A, B}, A3), and nucleotide receptors, P2X and P2Y receptors. Burnstock proposed calling the former the P1 receptor and the latter the P2 receptor(1978), and further subdividing the P2 receptor into ion channel-typed P2X and G protein-coupled P2Y(1985). P2X and P2Y are collectively called ATP receptors. Adenosine-3'-phosphate (ATP) is an agonist of P2X receptors. P2X molecules form a trimer acting as a single non-selective cation channel (Na⁺, K⁺, Ca²⁺). Seven types from P2X1 to P2X7 have been reported. All subunit molecules form homomer receptors, and some P2X molecules can form heteromers (P2X1 with P2X5, P2X2 with P2X3 or P2X6, and P2X4 with P2X6 or P2X7). Various subtypes are expressed in all tissues in the body, and utilize the difference in sensitivity (1 million times difference from nM to mM) to play an important individual physiological functions.
It's already been 61 years since Holton pointed out the relationship between ATP and pain (1959). Today, ATP is involved in a variety of nociceptive transmission through ATP receptor subtypes that are variously expressed in dorsal root ganglion (DRG) neurons, dorsal root ganglion neurons, spinal microglia, and the upper central nervous system.
Currently, drug discovery targeting ATP receptors is being carried out all over the world.