P2Y receptors are one of three families of extracellular receptors for purine and pyrimidine nucleotides involved in purinergic signaling. In heterologous expression systems, recombinant P2Y1, P2Y2, P2Y4, P2Y6 receptors couple to G proteins (mainly Gq) which, in turn, activate intracellular signaling cascades - mainly the phospholipase Cβ (PLCβ) isoform to mobilise intracellular Ca2+ ions. RT-PCR and Northern Blotting studies show a high expression of this receptor in spleen and placenta, followed by kidney, adipose, bone, lung, heart, brain and skeletal muscle. In mouse bone marrow-derived mast cells (mBMMCs) and in the human MC line LAD2, P2Y6 receptors cooperate with CysLT1R to promote cell survival and chemokine generation by a pathway involving reciprocal ligand-mediated cross-talk. In human, rat and mouse, P2Y6 expression is increased by the stress associated with intestinal inflammation, leading to the release of CXC chemokine ligand 8. In rabbit, the receptor functions by increasing osteoclast survival through the NFκB pathway.