CLONING OF A HUMAN PURINERGIC P2Y RECEPTOR-COUPLED TO PHOSPHOLIPASE-CAND ADENYLYL-CYCLASE

Clones encoding a new human P2Y receptor, provisionally called P2Y(11) , have been isolated from human placenta complementary DNA and genomic DNA libraries, The 1113-base pair open reading frame is interrupted b y one intron, The P2Y(11) receptor is characterized by considerably la rger second and third extracellular loops than the subtypes described so far. The deduced amino acid sequence exhibits 33% amino acid identi ty with the P2Y(1) receptor, its closest homolog. Northern blot analys is detected human P2Y(11) receptor messenger RNA in spleen and HL-60 c ells. The level of P2Y(11) transcripts was strongly increased in these cells after granulocyte differentiation induced by retinoic acid or d imethyl sulfoxide. The new receptor was stably expressed in 1321N1 ast rocytoma and CHO-K1 cells, where it couples to the stimulation of both the phosphoinositide and adenylyl cyclase pathways, a unique feature among the P2Y family. The rank order of agonists potency was: ATP > 8- methylthio-ATP >>> ADP, whereas UTP and UDP were inactive, indicating that it behaves as a selective purinoceptor.