The discovery and development of P2 receptor subtypes

Extracellular purine and pyrimidine nucleotides modulate cellular activity by acting at P2 receptors. The first receptor to be identified was the P₂-purinoceptor, which was characterised and named in 1978. In the 1980s this site was subdivided into P_2X and P_2Y purinoceptors on the basis of pharmacological criteria in functional studies on native receptors. Subsequently, a similar approach led to the characterisation of the P_2T, P_2Z, P_2U and P_2D purinoceptors. In the 1990s a molecular biological approach has led to the cloning and functional expression of at least 12 mammalian P2 receptor subtypes. The challenge now is to relate these recombinant receptors to native receptors present within a wide range of tissues.