Cloning, functional expression and tissue distribution of the human P2Y6 receptor

In order to isolate new subtypes of P2Y purinoceptors, a human placenta cDNA library was screened at middle stringency with a P2Y4 probe. The purification and the sequencing of several clones led us to identify a 984 base pair open reading frame encoding a new human P2Y receptor. It appeared later that this sequence corresponds to the human ortholog (88% amino acid identity) of the rat receptor recently cloned by Chang et al (J. Biol. Chem. 270, 26152-26158, 1995) and called P2Y6. Northern blot analysis detected human P2Y6 receptor messenger RNA in human spleen, placenta, thymus, intestine, and blood leukocytes. In 1321N1 cells stably expressing the human P2Y6 receptor, the formation of IP3 was stimulated by nucleotides with the following order of potency: UDP > 5-bromo-UPT > UTP > ADP > 2-methylthio-ATP >> ATP. The P2Y6 receptor, together with the previously cloned P2Y4 subtype (Communi et al., J. Biol. Chem., 270, 30849-30852, 1995), belongs thus to a subfamily of pyrimidinoceptors inside the P2Y family.