CLONING, FUNCTIONAL EXPRESSION AND TISSUE DISTRIBUTION OF THE HUMAN P2Y(6) RECEPTOR

In order to isolate new subtypes of P2Y purinoceptors, a human placent a cDNA library was screened at middle stringency with a P2Y(4) probe. The purification and the sequencing of several clones led us to identi fy a 984 base pair open reading frame encoding a new human P2Y recepto r. It appeared later that this sequence corresponds to the human ortho log (88% amino acid identity) of the rat receptor recently cloned by C hang et al (J. Biol. Chem. 270, 26152-26158, 1995) and called P2Y(6). Northern blot analysis detected human P2Y(6) receptor messenger RNA in human spleen, placenta, thymus, intestine, and blood leukocytes. In 1 321N1 cells stably expressing the human P2Y(6) receptor, the formation of IP3 was stimulated by nucleotides with the following order of pote ncy: UDP>5-bromo-UPT>UTP>ADP>2-methylthio-ATP much greater than The P2 (Y)6 receptor, together with the previously cloned P2Y(4) subtype (Com muni et al., J. Biol. Chem., 270, 30849-30852, 1995), belongs thus to a subfamily of pyrimidinoceptors inside the P2Y family. (C) 1996 Acade mic Press, Inc.