P2Y11 receptors: properties, distribution and functions

The P2Y11 receptor is a G protein-coupled receptor that is stimulated by endogenous purine nucleotides, particularly ATP. Amongst P2Y receptors it has several unique properties; 1) it is the only human P2Y receptor gene that contains an intron in the coding sequence; 2) the gene does not appear to be present in the rodent genome; 3) it couples to stimulation of both phospholipase C and adenylyl cyclase. Its absence in mice and rats, along with a limited range of selective pharmacological tools, has hampered the development of our knowledge and understanding of its properties and functions. Nonetheless, through a combination of careful use of the available tools, suppression of receptor expression using siRNA and genetic screening for SNPs, possible functions of native P2Y11 receptors have been identified in a variety of human cells and tissues. Many are in blood cells involved in inflammatory responses, consistent with extracellular ATP being a damage-associated signalling molecule in the immune system. Thus proposed potential therapeutic applications relate, in the main, to modulation of acute and chronic inflammatory responses.